PHARMACEUTICAL COMPOSITION FOR USE IN THE TREATMENT OR PREVENTION OF A C5-RELATED DISEASE AND METHOD FOR TREATING OR PREVENTING A C5-RELATED DISEASE

Abstract

The present invention relates to pharmaceutical compositions for use in the treatment or prevention of a C5-related disease and methods for treating or preventing a C5-related disease. The present invention further relates to dosages and administrations of anti-C5 antibodies or pharmaceutical compositions containing the antibody.

Description

PHARMACEUTICAL COMPOSITION FOR USE IN THE TREATMENT OR PREVENTION OF A C5-RELATED DISEASE AND METHOD FOR TO TREAT OR PREVENT A C5-RELATED DISEASE or Lcnnn / Lznz / E / YiAi Field of Invention The present invention relates to dosages and administrations of anti-C5 antibody. Background of the Invention The complement system plays a central role in suppressing immune complexes and in immune responses to infectious agents, foreign antigens, virus-infected cells, and tumor cells. There are approximately 25–30 complement proteins, which are found as a complex collection of plasma proteins and membrane cofactors. Complement components achieve their immune defense function through interaction with a series of intricate enzymatic cleavages and membrane-binding events. The resulting complement cascades lead to the production of products with opsonic, immunoregulatory, and lytic functions. Currently, a widely accepted fact is that the complement system can be activated through three different pathways: the classical pathway, the lectin pathway, and the alternative pathway. Ref. 313132 These pathways share many components, and although they differ in their initial stages, they converge and share the same terminal complement components (C5 to C9) responsible for the activation and destruction of target cells. The classical pathway is typically activated by the formation of antigen-antibody complexes. Regardless, the first step in the activation of the lectin pathway is the binding of specific lectins such as mannose-binding lectin (MBL), H-ficolin, M-ficolin, L-ficolin, and C-type lectin CL-11. In contrast, the alternative pathway spontaneously undergoes a low level of activation and turnover, which can be readily amplified on foreign or other abnormal surfaces (bacteria, yeast, virally infected cells, or damaged tissue). These pathways converge at a point where the C3 component of complement is cleaved by an active protease to yield C3a and C3b. C3a is an anaphylatoxin. C3b binds to bacterial and other cell types, as well as certain viruses and immune complexes, and tags them for removal from circulation (in this role they are known as opsonins). C3b also forms a complex with other components to form C5 convertase, which cleaves C5 to yield C5a and C5b. q Lcnnn / Lznz / E / YiAi C5 is a 190 kDa protein found in normal serum at approximately 80 pg / ml (0.4 μM). C5 is glycosylated, and approximately 1.5–3% of its mass is attributed to carbohydrates. Mature C5 is a 115 kDa heterodimeric alpha chain linked via disulfide bonds to a 75 kDa beta chain. C5 is synthesized as a single-chain precursor protein (proC5 precursor) of 1676 amino acids (see, for example, PTL1 and PTL2). The proC5 precursor is cleaved to provide the beta chain as an amino-terminal fragment and the alpha chain as a carboxy-terminal fragment. The polypeptide fragments of the alpha and beta chains are linked together via disulfide bonds and constitute the mature C5 protein. Mature C5 is cleaved into the C5a and C5b fragments during activation of complement pathways. C5a is cleaved from the C5 alpha chain by C5 convertase as an amino-terminal fragment comprising the first 74 amino acids of the alpha chain. The remaining portion of mature C5 is a C5b fragment, which contains the remainder of the alpha disulfide chain attached to the beta chain. Approximately 20% of the 11 kDa mass of C5a is attributed to carbohydrates. C5a is another anaphylatoxin. C5b combines with C6, C7, C8, and C9 to form the membrane attack complex (MAC, C5b-9, terminal complement complex (TCC)) on the surface of the target cell. When a sufficient number of MACs are inserted into the target cell membranes, the MACs form pores that mediate rapid osmotic lysis of the target cells. As mentioned earlier, C3a and C5a are anaphylatoxins. They can trigger mast cell degranulation, which releases histamine and other inflammatory mediators, resulting in smooth muscle contraction, increased vascular permeability, leukocyte activation, and other inflammatory phenomena, including cell proliferation leading to hypercellularity. C5a also functions as a chemotactic peptide that attracts granulocytes such as neutrophils, eosinophils, basophils, and monocytes to the complement activation site. The activity of C5a is regulated by the plasma enzyme carboxypeptidase N, which removes the carboxy-terminal arginine from C5a, forming a C5a-des-Arg derivative. C5a-des-Arg exhibits only 1% of the anaphylactic activity and polymorphonuclear chemotactic activity of unmodified C5a. Although a properly functioning complement system provides a robust defense against infectious microbes, inappropriate regulation or activation of complement has been linked to the pathogenesis of a variety of disorders, including, for example, rheumatoid arthritis (RA); lupus nephritis; ischemia-reperfusion injury; paroxysmal nocturnal hemoglobinuria (PNH); atypical hemolytic uremic syndrome (aHUS); dense deposit disease (DDD); macular degeneration (e.g., age-related macular degeneration (AMD)); hemolysis; elevated liver enzymes and low platelet syndrome (HELLP); and thrombotic thrombocytopenic purpura (TTP). Spontaneous fetal loss, pauci-immune vasculitis, epidermolysis bullosa;Recurrent fetal loss, multiple sclerosis (MS); traumatic brain injury, and injury resulting from myocardial infarction, cardiopulmonary bypass, and hemodialysis (see, for example, NPL1). Therefore, inhibition of excessive or uncontrolled activations of the complement cascade may provide clinical benefits to patients with such disorders. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder in which endangered red blood cells are destroyed more rapidly than normal red blood cells. PNH occurs as a result of clonal expansion of hematopoietic stem cells with somatic mutations in the PIG-A (phosphatidylinositol glycan class A) gene located on the X chromosome. Mutations in PIG-A lead to an early block in the synthesis of glycosylphosphatidylinositol (GPI), a molecule required for anchoring many proteins to the cell surface. Therefore, in PNH, blood cells are deficient in GPI-anchored proteins, including the complement regulatory proteins CD55 and CD59.Under normal circumstances, these complement regulatory proteins block the formation of MACs on the cell surface, thereby preventing erythrocyte lysis. The absence of GPI-anchored proteins causes complement-mediated hemolysis in PNH. PNH is characterized by hemolytic anemia (a reduction in the number of red blood cells), hemoglobinuria (the presence of hemoglobin in the urine, particularly evident after sleep), and hemoglobinemia (the presence of hemoglobin in the bloodstream). Individuals with PNH are known to experience paroxysms, defined here as episodes of dark-colored urine. The hemolytic anemia results from the intravascular destruction of red blood cells by complement components. Other known symptoms include dysphasia, fatigue, erectile dysfunction, thrombosis, and recurrent abdominal pain. Eculizumab is a humanized monoclonal antibody directed against the complement protein C5 and the first approved therapy for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) (see, for example, NPL2). Eculizumab inhibits the cleavage of C5 into C5a and C5b by C5 convertase, which prevents the generation of the terminal complement complex C5b-9. Both C5a and C5b-9 cause terminal complement-mediated events that are characteristic of PNH and aHUS (see also PTL3, PTL4, PTL5, and PTL6). Several reports have described anti-C5 antibodies. For example, PTL7 describes an anti-C5 antibody that binds to the alpha chain of C5 but not to C5a, and blocks C5 activation, while PTL8 describes an anti-C5 monoclonal antibody that inhibits C5a formation. PTL9, on the other hand, describes an anti-C5 antibody that recognizes the proteolytic site for C5 convertase on the alpha chain of C5 and inhibits the conversion of C5 to C5a and C5b. PTL10 describes an anti-C5 antibody with a constant affinity of at least 1 x 10⁷ M⁻¹. Antibodies (IgGs) bind to the neonatal iron receptor (FcRn) and have prolonged plasma retention times. IgG binding to FcRn is typically observed under acidic conditions (e.g., pH 6.0) and rarely under neutral conditions (e.g., pH 7.4). Typically, IgGs are nonspecifically taken up into cells by endocytosis and return to the cell surface by binding to endosomal FcRn under the acidic conditions of the endosome. IgGs then dissociate from FcRn under the neutral conditions of plasma. IgGs that fail to bind to FcRn are degraded in the lysosome. When the ability of an IgG to bind to FcRn under acidic conditions is eliminated by introducing mutations in its Fe region, the IgG is not recycled from the endosome to the plasma, causing a marked deficiency in the retention of IgG in plasma.To improve the plasma retention of IgG, a method has been reported that increases its FcRn binding under acidic conditions. When the FcRn binding of an IgG is enhanced under acidic conditions by introducing a one-amino acid substitution in its Fe region, the IgG is recycled more efficiently from the endosome to the plasma, thus exhibiting improved plasma retention. Meanwhile, it has also been reported that an IgG with enhanced FcRn binding under neutral conditions does not dissociate from FcRn under neutral plasma conditions, even when it returns to the cell surface via FcRn binding under the acidic conditions of the endosome, and therefore its plasma retention remains unchanged, or rather, worsens (see, for example, NPL3; NPL4; NPL5). Recently, antibodies that bind to antigens in a pH-dependent manner have been reported (see, for example, PTL11 and PTL12). Such antibodies bind tightly to antigens under the neutral conditions of plasma and dissociate from the antigens under the acidic conditions of the endosome. After dissociation from the antigens, the antibodies become capable of binding to the antigens again when they are recycled back into the plasma via FcRn. Thus, a single antibody molecule can repeatedly bind to multiple antigen molecules. In general, the plasma retention of an antigen is much shorter than that of an antibody with the aforementioned FcRn-mediated recycling mechanism. Therefore, when an antigen is bound to an antibody, the antigen typically exhibits prolonged plasma retention, resulting in an increased plasma concentration of the antigen.On the other hand, it has been reported that the previously described antibodies, which bind to antigens in a pH-dependent manner, clear antigens from the plasma more rapidly than typical antibodies because they dissociate from the antigens within the endosome during the FcRn-mediated recycling process. PTL13 also describes computer modeling analyses showing that a pH-dependent binding antibody directed against C5 can extend the agonistic antigen. o Lcnnn / Lznz / E / YiAi List of Appointments Patent Literature [PTL1] US Patent No. 6,355,245 [PTL2] US Patent No. 7,432,356 [PTL3] wo 2005 / 074607 [PTL4] wo 2007 / 106585 [PTL5] wo 2008 / 069889 [PTL6] wo 2010 / 054403 [PTL7] wo 95 / 29697 [PTL8] wo 2002 / 30985 [PLT9] wo 2004 / 007553 [PLT10] wo 2010 / 015608 [PTL11] wo 2009 / 125825 [PLT12] wo 2011 / 122011 [PTL13] wo 2011 / 111007 Non-Patent Literature [NPL1] Holers et al., Immunol, Rev. 223:300-316 (2008) [NPL2] Dmytrijuk et al., The Oncologist 13(9):9931000 (2008) [NPL3] Yeung et al., J Immunol. 182(12); 7663-7671 (2009) [NPL4] Datta-Mannan et al., J Biol. Chem. 282(3): 1709-1717 (2007) [NPL5] Dall'Acqua et al., J. Immunol. 169(9): 517111 5180 (2002) Brief Description of the Invention The invention provides pharmaceutical compositions for use in the treatment or prevention of a C5-related disease and methods for treating or preventing a C5-related disease. The invention also provides dosages and administrations of anti-C5 antibody or pharmaceutical compositions containing the anti-C5 antibody. The inventors of the invention are investigating effective anti-C5 antibody dosages and administrations for use in the treatment and / or prevention of C5-related diseases, which also reduces the burden on patients. Based on these findings, the inventors discovered that low-dose administration at least once before high-dose administration at prolonged intervals is advantageous for the treatment or prevention of a C5-related disease by subcutaneous administration of anti-C5 antibody. The inventors also discovered suitable dosing conditions, including antibody dose, frequency, and intervals of subcutaneous administrations. Specifically, the present invention relates to: A pharmaceutical composition for use in the treatment or prevention of a C5-related disease, wherein the composition is formulated for subcutaneous injection and comprises an anti-C5 antibody, wherein the other composition is administered subcutaneously in two phases, wherein in both phases there is an interval between each two subcutaneous administrations, wherein each phase comprises at least one interval, and wherein in the first phase... i) at least one interval is shorter than at least one interval in the second phase, and ii) the antibody dose per administration is lower than or the same as the antibody dose per administration in the second phase; The pharmaceutical composition for use DE [1] where at least one interval in the first phase is from 1 day to 2 months; The pharmaceutical composition to be used of [1] or [2], wherein at least one interval in the first phase is from 5 days to 14 days; The pharmaceutical composition to be used from any of [1] to [3], wherein at least one interval in the second phase is from 2 days to 6 months; q Lcnnn / Lznz / E / YiAi The pharmaceutical composition to be used from any of [1] to [4], wherein at least one interval in the second phase is from 15 days to 3 months; The pharmaceutical composition for use is any of [1] to [5], wherein the dose of the antibody in the first phase subcutaneous administration is 50 mg to 350 mg; The pharmaceutical composition for use is any of [1] to [6], wherein the antibody dose for subcutaneous administration in the first phase is 150 mg to 200 mg and lower than the dose for subcutaneous administration in the second phase, preferably wherein the antibody dose in the first phase is 170 mg; The pharmaceutical composition to be used from any of [1] to [6], wherein the antibody dose for subcutaneous administration in the first phase is 300 mg to 350 mg and the same as the antibody dose for subcutaneous administration in the second phase; The pharmaceutical composition for use is any of [1] to [8], wherein the number of subcutaneous administrations in the first phase is from 1 to 12; The pharmaceutical composition to be used from either one of [1] or [9], the number of subcutaneous administrations in the first phase is 5 to 10, preferably where the number is 8; o Lcnnn / Lznz / E / YiAi The pharmaceutical composition for use is any of [1] to

[10] , wherein the antibody dose per administration in the second phase is 350 mg to 1000 mg, or 650 mg to 700 mg; The pharmaceutical composition to be used from any of [1] to [7] and [9] to

[11] , wherein the C5 antibody per administration in the first phase is three to five times lower than the anti-C5 antibody dose per administration in the second phase; The pharmaceutical composition for use from any of [1] to

[12] , wherein a pharmaceutical composition formulated for intravenous administration and comprising an anti-C5 antibody is administered intravenously prior to the first subcutaneous administration of the first phase; The pharmaceutical composition to be used of

[13] , wherein the first subcutaneous administration of the first phase is administered 0 days to 1 month after the final administration of the pharmaceutical composition administered intravenously; The pharmaceutical composition for use of

[13] to

[14] , wherein the dose of the antibody for such intravenous administration is 100 to 2000 mg; The pharmaceutical composition for use from any one of [1] to

[15] , wherein the C5-related disease is any one selected from a group consisting of rheumatoid arthritis (RA); lupus nephritis; ischemic reperfusion injury; paroxysmal nocturnal hemoglobinuria (PNH); atypical hemolytic uremic syndrome (aHUS); dense deposit disease (DDD); macular degeneration; hemolysis, elevated liver enzymes and low platelet syndrome (HELLP); thrombotic thrombocytopenic purpura (TTP); spontaneous fetal loss; pauci-immune vasculitis; epidermolysis bullosa; recurrent fetal loss; multiple sclerosis (MS); traumatic brain injury; and injury resulting from myocardial infarction, cardiopulmonary bypass, or hemodialysis; The method for treating or preventing a C5-related disease, wherein the method comprises subcutaneously administering to a subject a pharmaceutical composition formulated for subcutaneous injection and comprising an anti-C5 antibody, wherein the composition is administered subcutaneously in two phases, wherein both phases have an interval between each two subcutaneous administrations, wherein each phase comprises at least one interval, and wherein the first phase i) at least one interval is shorter than at least one interval in the second phase, and ii) the antibody dose per administration is less than or equal to the antibody dose per administration in the second phase; o Lcnnn / Lznz / E / YiAi Use of an anti-C5 antibody in the manufacture of a pharmaceutical composition to treat or prevent a C5-related disease, wherein the composition is formulated for subcutaneous injection, comprises the anti-C5 antibody, and wherein the composition is administered subcutaneously in two phases, wherein in both phases there is an interval between each two subcutaneous administrations, wherein each phase comprises at least one interval, and wherein in the first phase (i) at least one interval is shorter than at least one interval in the second phase, and (ii) the antibody dose per administration is less than or equal to the antibody dose per administration in the second phase; and A product for treating or preventing a C5-related disease, comprising (a) a container; (b) a pharmaceutical composition in the container, wherein the pharmaceutical composition is formulated for subcutaneous injection and comprises an anti-C5 antibody; and (c) a document instructing that the pharmaceutical composition is administered subcutaneously in two phases, wherein in both phases there is an interval between each two subcutaneous administrations, wherein each phase comprises at least one interval, and wherein in the first phase q Lcnnn / Lznz / E / YiAi i) at least one interval is shorter than at least one interval in the second phase, and ii) the antibody dose per administration is less than or the same as the antibody dose per administration in the second phase. Brief Description of the Figures Figures 1A-1B show the change in plasma concentration of 305LO15 in cynomologist monkeys over time by subcutaneous injection (Figure 1A) or intravenous injection (Figure 1B) of the 305LO15 antibody. Plasma concentration of 305LO15 was measured by ELISA. Each data point shows a mean value from three males or three females in (Figure 1A) and a mean value from six males or six females in (Figure 1B). Figure 2 shows the change in plasma concentration of 305LO15 in cynomologist monkeys over time after the monkeys received an initial intravenous injection and subsequent subcutaneous maintenance injections of the 305LO15 antibody. Plasma concentration of 305LO15 was measured by ELISA. Each data point shows a mean value from five males or five females. Figure 3A is a graph in which the plasma concentrations of free C5 were plotted against each plasma concentration of the antibody for each amount and route, IV, intravenous injection; SC, subcutaneous injection; or Lcnnn / Lznz / E / YiAi. Figure 3B is a graph in which the measured complement activities were plotted against each antibody concentration for each indicated dosage amount and route. IV, intravenous injection; SC, subcutaneous injection. Figure 4A shows the simulated time courses of plasma concentration of 305LO15 in dosage regimens designed for the clinical study Part 1. IV, intravenous injection; SC, subcutaneous injection. Figure 4B shows the simulated time course of plasma concentration of 305LO15 under the dosing regimen designed for the clinical study Part 2. SC, subcutaneous injection; CS, once-weekly administration. Figure 4C shows the simulated time courses of plasma concentration of 305LO15 in dosing regimens designed for the Part 3 clinical study. SC, subcutaneous injection; CS, once-weekly administration; C2S, once-every-two-week administration; C4S, once-every-four-week administration. Figure 5 shows the profile of immune complexes formed with eculizumab (ECZ), human C5 (hC5), and / or 305LO15 analyzed by in vitro size exclusion chromatography at pH 7.4 (top) and pH 6.0 (bottom). Figure 6 shows the simulated and observed plasma concentration-time profiles of 305LO15 in healthy subjects who received a 75 mg IV infusion (over 60 min). The gray shaded area is the 95% prediction interval of the simulated 305LO15 concentration-time profile. The solid line indicated by an arrow is the simulated mean 305LO15 concentration-time profile. The dashed line denotes the 40 µg / mL PD threshold. Figure 7 shows the simulated and observed plasma time-concentration profiles of 305LO15 in healthy subjects who received a 125 mg IV infusion (over 60 min). The gray shaded area is the 95% prediction interval of the simulated 305LO15 time-concentration profile. The solid line indicated by an arrow is the simulated mean 305LO15 time-concentration profile. The dashed line denotes the 40 µg / mL PD threshold. Figure 8 shows the simulated and observed plasma time-concentration profiles of 305LO15 in healthy subjects who received 100 mg SC. The gray shaded area is a 95% prediction interval of the simulated 305LO15 time-concentration profile. The solid line indicated by an arrow is the simulated median 305LO15 time-concentration profile. For simulations conducted for a single 100 mg SC dose, a bioavailability of 90% is expected. The dashed line denotes the 40 µg / mL PD threshold. Figure 9 shows the relationship between plasma concentrations of 305LO15 and hemolytic activity (LIA) after a single SC injection or IV infusion in healthy subjects. The ex vivo LIA dose-response curve was generated using selected human plasma samples with various concentrations of 305LO15. Figure 10A shows the time profile of serum LDH levels in a PNH patient, patient X, who received an IV dose of 375 mg of 305LO15 on day 1, an IV dose of 500 mg of 305LO15 on day 8, an IV dose of 1000 mg of 305LO15 on day 22, a SC dose of 170 mg of 305LO15 on day 36, and a SC dose of 170 mg of 305LO15 on day 43 in the Part 2 study. Figure 10B shows the time-of-hemolytic activity (LIA) profile in patient PNH, patient X, who received an IV dose of 375 mg of 305LO15 on day 1, an IV dose of 500 mg of 305LO15 on day 8, an IV dose of 1000 mg of 305LO15 on day 22, an SC dose of 170 mg of 305LO15 on day 36, and an SC dose of 170 mg of 305LO15 on day 43 in the Part 2 study. Figure 11 shows the Se dose regimen optimized in Part 3 of study BP39144. Detailed Description of the Invention The techniques and procedures described or referenced herein are generally well understood and routinely employed using conventional methodology by experts in the field, such as, for example, the widely used methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual, 3rd edition (2001), Coid Spring Harbor Laboratory Press, Coid Spring Harbor, NY; Current Protocols in Molecular Biology (FM Ausubel, et al., eds., (2003)); and the series Methods in Enzymology (Academic Press, Inc.): PCR 2: A Practical Approach (M.J. MacPherson, B.D. Hames and G.R. Taylor eds. (1995)), Harlow and Lañe, eds. (1988) Antibodies, A Laboratory Manual, and Animal Cell Culture (R.I. Freshney, ed. (1987)); Oligonucleotide Synthesis (M.J. Gait, ed., 1984); Methods in Molecular Biology, Humana Press; Cell Biology: A Laboratory Notebook (J.E. Cellis, ed., 1998) Academic Press; Animal Cell Culture (R.I. Freshney), ed., 1987); Introduction to Cell and Tissue Culture (J. P. Mather and P.E. Roberts, 1998) Plenum Press; Cell and Tissue Culture: Laboratory Proceedings (A. Doyle, J.B. Griffiths, and D.G. Newell, eds., 1993-8) J. Wiley and Sons; Handbook of Experimental Immunology (D.M. Weir and C.C. Blackwell, eds.); Gene Transfer Vectors for Mammalian Cells (J.M. Miller and M.P. Calos, eds., 1987); PCR: The Polymerase Chain Reaction, q Lcnnn / Lznz / E / YiAi (Mullís et al., eds., 1994); Current Protocols in Immunology (J.E. Coligan et al., eds., 1991); Short Protocols in. Molecular Biology (Wiley and Sons, 1999); Immunobiology (CA Janeway and P. Travers, 1997); Antibodies (P. Finch, 1997); Antibodies: A Practical Approach (D. Catty., ed., IRL Press, 1988-1989); Monoclonal Antibodies: A Practical Approach (P. Shepherd and C. Dean, eds., Oxford University Press, 2000); Using Antibodies: A Laboratory Manual (E. Harlow and D. Lañe (Coid Spring Harbor Laboratory Press, 1999); Antibodies (M. Zanetti and JD Capra, eds., Harwood Academic Publishers, 1995); and Cancer: Principles and Practice of Oncology (VT DeVita et al., eds., JB Lippincott Company, 1993). I. Definition Interval (an interval between individual administrations) indicates an interval between the administration of dose n (n is an integer of 1 or greater) and administration of dose n(+l). II. A pharmaceutical composition for subcutaneous injection A pharmaceutical composition is provided for use in a method of treating or preventing a C5-related disease. The pharmaceutical composition is formulated for subcutaneous injection and comprises an anti-C5 antibody, wherein the composition is administered subcutaneously in two phases, wherein in both phases there is an interval between each two subcutaneous administrations, wherein each phase comprises at least one interval, and wherein in the first phase (i) at least one interval is shorter than at least one interval in the second phase, and (ii) the dose of the antibody per administration is less than or the same as the dose of the antibody per administration in the second phase. Subcutaneous injection can be performed using standard devices and methods for administering a pharmaceutical composition into subcutaneous tissue by injection. Devices and methods specifically designed for subcutaneous injection can also be selected. Anti-C5 Antibodies Samples The anti-C5 antibody is not limited to a specific modality and can be appropriately selected from antibodies known as anti-C5 antibodies. The term anti-C5 antibody, or an antibody that binds to C5, refers to an antibody that is capable of binding to C5 with sufficient affinity that the antibody is useful as a therapeutic agent targeting C5. In one aspect, anti-C5 antibodies inhibit C5 activation. In certain modes, anti-C5 antibodies prevent the cleavage of C5 to form C5a and C5b, thereby preventing the generation of anaphylactic activity associated with C5a, as well as preventing the assembly of the C5b-9 membrane attack complex (MAC) associated with C5b. In certain modes, anti-C5 antibodies block the conversion of C5 to C5a and C5b by C5 convertase. In certain modes, anti-C5 antibodies block access of C5 convertase to the cleavage site on C5. In certain modes, anti-C5 antibodies block hemolytic activity caused by C5 activation. In additional modes, anti-C5 antibodies inhibit C5 activation via the classical and / or alternative pathways. In one aspect, the pharmaceutical compositions of the present invention are useful in treating or preventing a C5-related disease in at least one part based on the aforementioned activities of anti-C5 antibodies in inhibiting C5 activity. In certain modalities, C5 activity can be measured as a function of its ability to lyse cells in the subject's body fluids. The ability of C5 to lyse cells, or a reduction thereof, can be measured by methods well known in the art, for example, a conventional hemolytic assay, such as the hemolysis assay described by Kabat and Mayer (eds), Experimental Immunochemistry, 2nd Edition, 135-240, Springfield, IL, CC Thomas (1961), pages 135-139, or a conventional variation of the assay, such as the method of chicken erythrocyte hemolysis as described in, for example, Hillmen et al., N. Engl. J. Med. 350(6): 552-559 (2004). In certain modalities, C5 activity, or its inhibition, is quantified using a CH50eq assay. The CH50eq assay is a method for measuring the classical activity of total complement in serum.This test is a Utico assay, which uses antibody-sensitized erythrocytes as the activator of the classical complement pathway and various dilutions of the test serum to determine the amount required to produce 50% lysis (CH50). The percentage of hemolysis can be determined, for example, using a spectrophotometer. The CH50eq assay provides an indirect measure of terminal complement complex (TCC) formation, since TCCs are directly responsible for the measured hemolysis. Inhibition of C5 activation can also be detected and / or measured using the methods described and exemplified in the working examples. Using these or other suitable assay types, candidate antibodies capable of inhibiting C5 activation can be selected.In certain modalities, inhibition of C5 activity includes at least a 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% or greater decrease in C5 activation in an assay compared to the effect of a negative control under similar conditions. In some modalities, it refers to the inhibition of C5 activation by at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% or more. In preferred modalities, an anti-C5 antibody epitope is different from the eculizumab epitope. In certain embodiments, the anti-C5 antibody of the present invention binds to an epitope within the beta chain of C5. In certain embodiments, the anti-C5 antibody binds to an epitope within the MG1-MG2 domain of the beta chain of C5. In certain embodiments, the anti-C5 antibody binds to an epitope within a fragment consisting of amino acids 19-180 of the beta chain of C5. In certain embodiments, the anti-C5 antibody binds to an epitope within the MG1 domain (amino acids 20-124 of SEC. ID NO.: 1) of the beta chain of C5. In certain embodiments, the anti-C5 antibody binds to an epitope within a fragment consisting of amino acids 33-124 of the beta chain of C5 (SEC. ID NO.: 1). In certain embodiments, an anti-C5 antibody of the present invention binds to an epitope within the beta chain of C5, which consists of the MG1 domain. In certain embodiments, an anti-C5 antibody binds to an epitope within the beta chain (SEC. ID NO.: 1) of C5, which comprises at least one fragment selected from the group consisting of amino acids 47-57, 70-76, and 107-110. In certain embodiments, an anti-C5 antibody binds to an epitope within a fragment of the beta chain (SEC. ID NO.: 1) of C5 which comprises at least one amino acid selected from the group consisting of Thr47, Glu48, Ala49, Phe50, Asp51, Ala52, Thr53, Lys57, His70, Val71, His72, Ser74, Glu76, Vall07, Serl08, Lysl09, and Hisl0. In certain embodiments, an anti-C5 antibody binds to an epitope within a fragment of the beta chain (SEC. ID NO.1) of C5 comprising at least one amino acid selected from the group consisting of Glu48, Asp51, His70, His72, Lysl09, and Hisl0. In certain embodiments, the binding of an anti-C5 antibody to a mutant C5 is reduced compared to its binding to wild-type C5, wherein the mutant C5 has at least one amino acid substitution at a position selected from the group consisting of Glu48, Asp51, His72, and Lysl09. In another embodiment, the pH-dependent binding (described below) of an anti-C5 antibody to a mutant C5 is reduced compared to its pH-dependent binding to wild-type C5, wherein the mutant C5 has at least one amino acid substitution at a position selected from the group consisting of His70, His72, and Hisl0.In an additional embodiment, an amino acid at a selected position from Glu48, Asp51, and Lysl09 is substituted with alanine, and an amino acid at a selected position from His70, His72, and HisllO is substituted with tyrosine in the mutant O5. o Lcnnn / Lznz / E / YiAi In another aspect, the anti-C5 antibodies of the present invention may exhibit pH-dependent binding characteristics. As used herein, the term pH-dependent binding means that the antibody exhibits reduced binding to C5 at acidic pH compared to its binding at neutral pH (for the purposes of this description, both terms may be used interchangeably). For example, antibodies with pH-dependent binding characteristics include antibodies that bind to C5 with higher affinity at neutral pH than at acidic pH. In certain embodiments, the antibodies bind to C5 with at least 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000, or more times greater affinity at neutral pH than at acidic pH. In some forms, the antibodies bind to C5 with greater affinity at pH 7.4 than at pH 5.8. In additional forms, the antibodies bind to C5 with at least 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000, or more times greater affinity at pH 7.4 than at pH 5.8. The affinity of an antibody for C5, for the purposes of this description, is expressed in terms of the antibody's Kd. The Kd of an antibody refers to the equilibrium dissociation constant of an antibody-antigen interaction. The higher the Kd value of an antibody's binding to its antigen, the weaker its binding affinity for that particular antigen. Accordingly, as used herein, the expression "higher affinity at neutral pH than at acidic pH" (or the equivalent expression "pH-dependent binding") means that the Kd for the antibody's binding to C5 at acidic pH is greater than the Kd for the antibody's binding to C5 at neutral pH. For example, in the context of the present invention, an antibody is considered to bind to C5 with a higher affinity at neutral pH than at acidic pH if the Kd of the antibody binding to C5 at acidic pH is at least twice as high as the Kd of the antibody binding to C5 at neutral pH.Thus, the anti-C5 antibody of the present invention includes antibodies that bind to C5 at acidic pH with a KD that is at least 2, 3, 5, 10, 15, 20, 25, 30, 35. 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000, or more times greater than the KD of the antibody that binds to C5 at neutral pH. In another embodiment, the KD value of the antibody at neutral pH may be 10⁻⁷M, 10⁻⁸M, 10⁻⁹M, 10⁻¹⁰M, 10⁻¹¹M, 10⁻¹²M, or less. In another embodiment, the KD value of the antibody at acidic pH may be 10⁻⁹M, 10⁻⁸M, 10⁻⁷M, 10⁻⁶M, or greater. In additional modalities, an antibody is considered to bind to C5 with greater affinity at a neutral pH than at an acidic pH if the KD of the antibody that binds to C5 at pH 5.8 is at least 2 times greater than the KD of the antibody that binds to C5 at pH 7.4. In some formulations, the antibodies bind to C5 at pH 5.8 with a KD that is at least 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000, or more times greater than the KD of the antibody that binds to C5 at pH 7.4. In another formulation, the KD value of the antibody at pH 7.4 may be 10⁻⁷M, 10⁻⁸M, 10⁻⁹M, 10⁻¹⁰M, 10⁻¹¹M, 10⁻¹²M, or less. In another modality, the KD value of the antibody at pH 5.8 can be 10~9M, 10~8M, 10~7M, 10~6M, or higher. The binding properties of an antibody to a particular antigen can also be expressed in terms of the antibody's kd. The kd of an antibody refers to the constant rate of dissociation of the antibody with respect to a particular antigen and is expressed in reciprocal seconds (i.e., s⁻¹). An increase in the kd value signifies a weaker binding of an antibody to its antigen. The present invention therefore includes antibodies that bind to C5 with a higher kd value at acidic pH than at neutral pH. The present invention includes antibodies that bind to C5 at an acidic pH with a kd that is at least 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000, or more times greater than the kd of the antibody that binds to C5 at a neutral pH. In another embodiment, the kd value of the antibody at a neutral pH may be 10⁻² µs, 10⁻³ µs, 10⁻⁴ µs, 10⁻⁵ µs, 10⁻⁶ µs, or less.In another embodiment, the kd value of the antibody at an acidic pH can be 10⁻³ 1 / s, 10⁻² 1 / s, 10⁻¹ 1 / s, or higher. The antibodies of the present invention also include antibodies that bind to C5 with a higher kd value at pH 5.8 than at pH 7.4. The antibodies of the present invention include antibodies that bind to C5 at pH 5.8 with a kd that is at least 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85. 90, 95, 100, 200, 400, 1000, 10000, or more times greater than the kd of the antibody that binds to C5 at pH 7.4. In another form, the kd value of the antibody at pH 7.4 may be 1Gb21 / s, 1Gb31 / s, 1Gb41 / s, ICb51 / s, 10~61 / s, or less. In another modality, the kd value of the antibody at pH 5.8 may be 10~31 / s, 10~21 / s, 1Gb11 / s, or greater. In some cases, reduced C5 binding at acidic pH compared to binding at neutral pH is expressed in terms of the ratio of the KD value of antibody binding to C5 at acidic pH to the KD value of antibody binding to C5 at neutral pH (or vice versa). For example, an antibody may be considered to exhibit reduced C5 binding at acidic pH compared to binding at neutral pH, for the purposes of the present invention, if the antibody has an acidic / neutral KD ratio of 2 or greater. In certain exemplary embodiments, the pH 5.8 / pH 7.4 KD or Lcnnn / Lznz / E / YiAi ratio for an antibody is 2 or greater. In certain exemplary modalities, the acidic / neutral KD ratio for an antibody may be 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000, or greater.In another embodiment, the KD value of the antibody at neutral pH may be 10⁻⁷ M, 10⁻⁸ M, 10⁻⁹ M, 10⁻¹⁰ M, 10⁻¹¹ M, 10⁻¹² M, or less. In another embodiment, the KD value of the antibody at acidic pH may be 10⁻⁹ M, 10⁻⁸ M, 10⁻⁷ M, 10⁻⁶ M, or greater. In further cases, an antibody exhibiting reduced C5 binding at acidic pH compared to its binding at neutral pH may be considered, for the purposes of the present invention, to have a KD pH 5.8 / pH 7.4 ratio of 2 or greater. In certain exemplary embodiments, the pH 5.8 / pH 7.4 KD ratio for an antibody of the present invention may be 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000, or higher. In another modality, the kd value of the antibody at pH. 7.4 can be 10⁻⁷ M, 10⁻⁸ M, 10⁻⁹ M, 10⁻¹⁰ M, 10⁻¹¹ M, 10⁻¹² M, or less. Alternatively, the kd value of the antibody at pH 5.8 can be 10~9M, 10~8M, 10~7M, 10~6M, or greater.In some cases, reduced C5 binding at acidic pH compared to binding at neutral pH is expressed in terms of the ratio of the antibody's C5 binding kd value at acidic pH to the antibody's C5 binding kd value at neutral pH (or vice versa). For example, an antibody may be considered to exhibit reduced C5 binding at acidic pH compared to binding at neutral pH, for the purposes of the present invention, if the antibody has an acid / neutral kd ratio of 2 or greater. In certain exemplary embodiments, the pH 5.8 / pH 7.4 kd ratio for an antibody is 2 or greater. In certain exemplary embodiments, the acid / neutral kd ratio for an antibody of the present invention may be 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000, or greater. In additional exemplary embodiments, the kd ratio is pH 5.8 / pH 7.4 for an antibody of the present invention may be 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200. 400, 1000, 10000, or greater. In another modality, the kd value of the antibody at a neutral pH can be 10~21 / s, 10~31 / s, 10⁻⁴ 1 / s, 10⁻⁵ 1 / s, 10⁻⁶ 1 / s, or less. In an additional mode, the antibody kd value at pH 7.4 may be 10⁻² 1 / s, 10⁻³ 1 / s, 10⁻⁴ 1 / s, 10⁻⁵ 1 / s, 10⁻⁶ 1 / s, or less. In another mode, the antibody kd value at an acidic pH may be 10⁻³ 1 / s, 10⁻² 1 / s, 10⁻¹ 1 / s, or greater. In an additional mode, the antibody kd value at pH 5.8 may be 10⁻³ 1 / s, 10⁻² 1 / s, 10⁻¹ 1 / s, or greater. As used herein, the expression acidic pH means a pH of 4.0 to 6.5. The expression acidic pH includes pH values ​​of any of 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, and 6.5. In this context, acidic pH is 5.8. As used herein, the expression pH neutral means a pH between 6.7 and approximately 10.0. The expression pH neutral includes pH values ​​of any of the following: 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, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, and 10.0. In this context, pH neutral is 7.4. The KD and kd values, as expressed herein, can be determined using a surface plasmon resonance-based biosensor to characterize antibody-antigen interactions. The KD and kd values ​​can be determined at 25°C or 37°C. In another aspect, an anti-C5 antibody comprises a heavy chain variable domain (HV) sequence that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with the amino acid sequence of SEC. ID NO.: 2. In certain embodiments, the HV sequence is the amino acid sequence of SEC. ID NO.: 2. In certain embodiments, a VH sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but an anti-C5 antibody comprising such a sequence retains the ability to bind to C5. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted, and / or deleted in the sequence. ID NO.: 2. In certain embodiments, the substitutions, insertions, or deletions occur in regions outside the HVRs (i.e., in the FRs).Optionally, the anti-C5 antibody comprises the VH sequence in SEC. ID NO.: 2, which includes post-translational modifications of that sequence. In one particular embodiment, the VH comprises one, two, or three HVRs selected from: (a) an HVR-H1 comprising the amino acid sequence in SEC. ID NO.: 3, (b) an HVR-H2 comprising the amino acid sequence in SEC. ID NO.: 4, and (c) an HVR-H3 comprising the amino acid sequence in SEC. ID NO.: 5. As used herein, the term HVR stands for hypervariable region and the term FR stands for scaffold. The framework or FR refers to the variable domain residues other than the hypervariable region (HVR) residues. The FR of a variable domain generally consists of four FR domains: FR1, FR2, FR3, and FR4. Therefore, the HVR and FR sequences generally appear in the following sequence in VH (or VL): FR1-H1(L1)-FR2-H2(L2)-FR3-H3(L3)-FR4. The term hypervariable region or HVR, as used herein, refers to each of the regions of an antibody variable domain that are hypervariable in sequence (complementarity-determining regions or CDRs) and / or form structurally defined loops (hypervariable loops) and / or contain antigen-contacting residues (antigen contacts). In general, antibodies comprise six HVRs: three in the VH (H1, H2, H3) and three in the VL (L1, L2, L3). Examples of HVRs include: (a) hypervariable loops that are present at amino acid residues 26-32 (L1), 50-52 (L2), 91-96 (L3), 26-32 (H1), 53-55 (H2), and 96-101 (H3) (Chothia, J. Mol. Biol. 196:901-917 (1987) ); (b) CDRs originating from amino acid residues 24-34 (L1), 50-56 (L2), 89-97 (L3), 31-35b (H1), 50-65 (H2) and 95-102 (H3) (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, NIH, Bethesda, MD (1991)); (c) antigen contacts originating from amino acid residues 27c-36 (L1), 46-55 (L2), 89-96 (L3), 30-35b (H1), 47-58 (H2) and 93-101 (H3) (MacCallum et al. J. Mol. Biol. 262:732-745 (1996)); and (d) combinations of (a), (b) and / or (c), including the HVR 4 amino acid residues 6-56 (L2), 47-56 (L2), 48-56 (L2), 49-56 (L2), 26-35 (Hl), 26-35b (Hl), 49-65 (H2), 93-102 (H3) and 94-102 (H3) (MacCallum et al. o Lcnnn / Lznz / E / YiAi J. Mol. Biol. 262:732-745 (1996)); and (d) combinations of (a), (b), and / or (c), which include the amino acid residues of HVR 46-56 (L2), 47-56 (L2), 48-56 (L2), 49-56 (L2), 26-35 (Hl), 26-35b (H1), 49-65 (H2), 93-102 (H3), and 94-102 (H3). HVR residues and other residues in the variable domain (e.g., FR residues) are numbered herein in accordance with Kabat et al., supra. In another aspect, an anti-C5 antibody comprises a light chain (VL) variable domain that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with the amino acid sequence of SEC. ID NO.: 6. In certain embodiments, the VL sequence is the amino acid sequence of SEC. ID NO.: 6. In certain embodiments, a VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but an anti-C5 antibody comprising such a sequence retains the ability to bind to O5. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted, and / or deleted in the SEC. ID NO.: 6. In certain embodiments, the substitutions, insertions, or deletions occur in regions outside the HVRs (i.e., in the FRs). Optionally, the anti-C5 antibody comprises the VL sequence in SEO. ID NO.: 6, including post-translational modifications of such sequence. In one particular embodiment, the VL comprises one, two, or three HVRs selected from (a) an HVR-L1 comprising the amino acid sequence of SEO. ID NO.: 7; (b) an HVR-L2 comprising the amino acid sequence of SEO. ID NO.: 8; and (c) an HVR-L3 comprising the amino acid sequence of SEO. ID NO.: 9. In another embodiment, the antibody is a full-length antibody, for example, an intact IgG1, IgG2, IgG3, or IgG4 antibody, or an antibody genetically engineered to have regions from two or more IgGs selected from IgG1, IgG2, IgG3, and IgG4 within the homologous region(s) between IgG subclasses by recombination. The antibody may comprise any suitable Fe region comprising a human Fe region sequence (for example, a human Fe IgG1, IgG2, IgG3, or IgG4 region). Region Fe variants In certain embodiments, an anti-C5 antibody according to the present invention comprises a variant Fe region in or Lcnnn / Lznz / E / YiAi in which one or more amino acid modifications have been introduced into a native sequence Fe region of an antibody. The variant Fe region may comprise a human Fe region sequence (e.g., a human IgG1, IgG2, IgG3, or IgG4 Fe region) comprising an amino acid modification (e.g., a substitution) at one or more amino acid positions. In certain embodiments, the invention contemplates a variant antibody that possesses some, but not all, of the effector functions, making it a desirable candidate for applications where the antibody's in vivo half-life is important, even though certain effector functions (e.g., complement and ADCC) are unnecessary or detrimental. In vitro and / or in vivo cytotoxicity assays can be performed to confirm the reduction / depletion of CDC and / or ADCC activities. For example, iron receptor (FcR) binding assays can be performed to ensure that the antibody lacks binding to Fe gamma R (and therefore likely lacks ADCC activity) but retains the ability to bind to FcRn. The primary cells that mediate ADCC, NK cells, express only Fe gamma RUI, while monocytes express Fe gamma RI, Fe gamma RII, and Fe gamma RUI.FcR expression in hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol. 9:457-492 (1991). Non-limiting examples of in vitro assays for evaluating the ADCC activity of a molecule of interest are described in U.S. Patent No. 5,500,362 (see, for example, Hellstrom et al., Proc. Nat'l Acad. Sci. USA 83:7059-7063 (1986)) and Hellstrom et al., Proc. Nat'l Acad. Sci. USA 82:1499-1502 (1985); U.S. Patent No. 5,821,337 (see Bruggemann et al., J. Exp. Med. 166:1351-1361 (1987)). Alternatively, non-radioactive assay methods can be employed (see, for example, the ACTI™ Non-Radioactive Cytotoxicity Assay for Flow Cytometry (CellTechnology, Inc., Mountain View, CA); and the CytoTox 96® Non-Radioactive Cytotoxicity Assay (registered trademark) (Promega, Madison, WI)). Useful effector cells for the assays include peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cells. Alternatively, or additionally, the ADCC activity of the molecules of interest can be evaluated in vivo, for example, in an animal model such as that described in Clynes et al., Proc. Nat'l Acad. Sci. USA 95:652-656 (1998). Clq binding assays can also be performed to confirm that the antibody is unable to bind to Clq and therefore lacks CDC activity. See, for example, ELISA binding assay of Clq and C3c in documents WO 2006 / 029879 and WO 2005 / 100402.To assess complement activation, a CDC assay can be performed (see, for example, Lcnnn / Lznz / E / YiAi). Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996); Cragg et al., Blood 101:1045-1052 (2003); and Cragg et al., Blood 103:2738-2743 (2004)). FcRn binding and in vivo suppression / half-life determinations can also be carried out using methods known in the technique (see, for example, Petkova et al., Int'l. Immunol. 18(12):1759-1769 (2006)). Antibodies with reduced effector function include those with substitution of one or more of the residues in the Fe region 238, 265, 269, 270, 297, 327, and 329 (U.S. Patent No. 6,737,056). Such Fe mutants include Fe mutants with substitutions at two or more of the amino acid positions 265, 269, 270, 297, and 327, including the so-called Fe DANA mutants with alanine substitution of residues 265 and 297 (U.S. Patent No. 7,332,581). Certain antibody variants with enhanced or reduced FcR binding have been described. (See, for example, U.S. Patent No. 6,737,056; WO 2004 / 056312, and Shields et al., J. Biol. Chem. 9(2):6591-6604 (2001)). In certain embodiments, a variant antibody comprises an Fe region with one or more amino acid substitutions that enhance ADCC, e.g., substitutions at positions 298, 333, and / or 334 of the Fe region (EU Residue Numbering). In some modalities, alterations are made to the Fe region that result in Complement-Dependent Cytotoxicity (CDC) and / or altered Clq binding (i.e., either enhanced or diminished), for example, as described in U.S. Patent No. 6,194,551, WO 1999 / 51642, and Idusogie et al., J. Immunol. 164:4178-4184 (2000). Antibodies with increased half-lives and improved binding to the neonatal Fe receptor (FcRn), which is responsible for the transfer of maternal IgGs to the fetus (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994)), have been described in US2005 / 0014934 (Hinton et al.). These antibodies comprise an Fe region with one or more substitutions that enhance the binding of the Fe region to FcRn. Such Fe variants include those with substitutions in one or more of the residues of the Fe region: 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, ​​413, 424 or 434, for example, substitution of residue 434 of the Fe region (U.S. Patent No. 7,371,826). See also Duncan, Nature 322:738-40 (1988); U.S. Patent No. 5,648,260; U.S. Patent No. 5,624,821; and WO 1994 / 29351 concerning other examples of variants of the Fe region. In certain embodiments, an anti-C5 antibody by or Lcnnn / Lznz / E / YiAi of the present invention comprises a VH as in any of the embodiments provided above and a heavy chain constant region comprising the amino acid sequence of any of the SEC. ID NOS.: 10, 11, 12, 13, 14, and 15. In certain embodiments, an anti-C5 antibody comprises a VL as in any of the embodiments provided above and a light chain constant region comprising the amino acid sequence of any of the SEC. ID NOS.: 16, 17, and 18. In certain embodiments, an anti-C5 antibody by the present invention is any of the antibodies described in documents WO2016 / 098356, WO2017 / 123636, and WO2017 / 132259. Subcutaneous administration The compositions for use of the present invention are administered subcutaneously in two phases. In both phases, there is an interval between each two subcutaneous administrations. Each phase comprises at least one interval. The last interval of the first phase is between the last subcutaneous administration of the first phase and the first subcutaneous administration of the second phase. In certain modalities, at least one interval in the first phase is from 1 day to 2 months. An appropriate interval in the first phase can be determined within a suitable range according to the conditions of a subject or a patient. The specific administration interval between subcutaneous injections is 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, or 42 days. In preferred modalities, the interval in the first phase is from 4 days to 35 days. In additional preferred modes, the interval in the first phase is 5 to 14 days. In highly preferred modes, the interval in the first phase is 7 to 14 days.The pharmaceutical composition can be administered every week (weekly), or once every two weeks (every two weeks or bi-weekly), in the first phase. In certain modalities, at least one interval in the second phase is between 2 days and 6 months. An appropriate duration for at least one interval in the second phase can be determined within a suitable range according to the conditions of a subject or patient. An exemplary duration of at least one interval in the second phase is 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 19 days, 20 days, 21 days, 25 days, 26 days, 27 days, 32 days, 33 days, 34 days, 38 days, 39 days, 40 days, 45 days, 46 days, 47 days, 51 days, 52 days, 53 days, 58 days, 59 days, 60 days, 64 days days, 65 days, 66 days, 71 days, 72 days, 73 days, 77 days, 78 days, 79 days, 84 days, 85 days, 86 days, 90 days, 91 days, 92 days, 22 days, 23 days, 24 days, 29 days, 30 days, 35 days36 days, 37 days, 42 days, 43 days, days, 48 ​​days, 49 days, 50 days, 55 days, 56 days, days, 61 days, 62 days, 63 days, 68 days, 69 days, days, 74 days, 75 days, 76 days, 81 days, 82 days, days, 87 days, 88 days, 89 days, 94 days, 95 days, q Lcnnn / Lznz / E / YiAi days, 97 days, 98 days, 99 days, 100 days, 101 days, 102 days, 103 days, 104 days, 105 days, 106 days, 107 days, 108 days, 109 days, 110 days, 111 days, 112 days, 113 days, 114 days, 115 days, 116 days 117 days, 118 days, 119 days, 120 days, 121 days, 122 days, 123 days, 124 days, 125 days, 126 days, 127 days, 128 days, 129 days, 130 days, 131 days, 132 days, 133 days 134 days, 135 days, 136 days, 137 days, 138 days, 139 days, 140 days, 141 days, days, 145 days, 146 days, 147 days, days, 151 days, 152 days, 153 days, 142 days, 143 days, 144 148 days, 149 days, 150 154 days, 155 days, 156 days, 157 days, 158 days, 159 days, days, 163 days, 164 days, 165 days, days, 169 days, 170 days, 171 days, 160 days, 161 days, 162 166 days, 167 days, 168 172 days, 173 days, 174 days, 175 days, 176 days, 177 days, 178 days, 179 days, 180 days, 181 days, 182 days, 183 days, or 184 days. In preferred modalities, the duration of at least one interval of the second phase is from 15 days to 3 months. In the second phase, the pharmaceutical composition may be administered once a month (monthly), once every two months (bimonthly), or once every three months (quarterly). The longer duration may reduce the burden or suffering of the patient. In certain modalities, the pharmaceutical composition is administered subcutaneously at a dose of 17 to 6,000 mg of the antibody in the first and second phases. An appropriate dose can be determined within a suitable range according to the individual's condition. If the pharmaceutical composition is administered subcutaneously to a subject repeatedly, the doses do not have to be the same each time and can be determined within the appropriate range. For example, the dose can be gradually reduced. In certain formulations, the first-phase subcutaneous dose is 50 to 350 mg of the antibody. When the first-phase subcutaneous antibody dose is lower than the second-phase subcutaneous antibody dose, the first-phase subcutaneous antibody dose is preferably 150 to 200 mg. A specific preferred dose is 170 mg in this case. When the first-phase subcutaneous antibody dose is the same as the second-phase subcutaneous antibody dose, the first-phase subcutaneous dose is preferably 300 to 350 mg of the antibody. A specific preferred dose is 340 mg in this case. When the pharmaceutical composition is administered weekly (at approximately 7-day intervals) in the first phase, a preferred dose is either 170 mg or 340 mg.When the pharmaceutical composition is administered every two weeks (with approximately 14 days between doses) in the first phase, a preferred dose is 340 mg. In preferred modalities, the antibody dose per administration in the second phase is 350 mg to 1,000 mg. In preferred modalities, the dose is 650 to 700 mg. When the pharmaceutical composition is administered every four weeks (within approximately 28 days of each other) or monthly, a preferred dose is 680 mg. The dosage regimen of a subcutaneous administration of 680 mg of antibody every four weeks or monthly may be particularly preferred, as it may reduce the burden or discomfort for the patient. In certain modalities, the dose of the anti-C5 antibody or Lcnnn / Lznz / E / YiAi administered in the first phase is three to five times lower than the dose of the anti-C5 antibody administered in the second phase. In preferred modalities, the dose of the antibody administered subcutaneously in the first phase is four times lower than the dose of the antibody administered subcutaneously in the second phase. In certain modalities, the number of subcutaneous administrations in the first phase is 1 to 12. In preferred modalities, the number is 5 to 10 times. In additional preferred modalities, there are 8 subcutaneous administrations in the first phase. In one embodiment, any pharmaceutically acceptable carrier available for a standard subcutaneous injection composition may be included in the pharmaceutical composition. A carrier type used for subcutaneous injection may be appropriately selected from carriers generally known in the art. In one sense, a pharmaceutical formulation can be any of the following: liquid, semisolid, and solid. The solid formulation is usually prepared by lyophilization from a liquid formulation. The lyophilized formulation is typically reconstituted using only water or saline solution prior to subcutaneous injection. o Lcnnn / Lznz / E / YiAi When the composition is administered subcutaneously, a concentration of the anti-C5 antibody in a liquid formulation of the composition is determined within a standard range in the technique. In one modality, a volume of the composition for subcutaneous injection is determined within a standard range in the technique. In certain forms, the disease related to C5 is a complement-mediated disease or condition which involves excessive or uncontrolled activation of C5.In certain modalities, the C5-related disease is at least one selected from a group consisting of rheumatoid arthritis (RA); lupus nephritis; ischemia-reperfusion injury; paroxysmal nocturnal hemoglobinuria (PNH); atypical hemolytic uremic syndrome (aHUS); dense deposit disease (DDD); macular degeneration; hemolysis, elevated liver enzymes, and low platelet syndrome (HELLP); thrombotic thrombocytopenic purpura (TTP); spontaneous fetal loss; pauci-immune vasculitis; epidermolysis bullosa; recurrent fetal loss; multiple sclerosis (MS); traumatic brain injury; and injury resulting from myocardial infarction, cardiopulmonary bypass, or hemodialysis; and generalized refractory myasthenia gravis (gMG). neuromyelitis optica (NMO). o Lcnnn / Lznz / E / YiAi In a preferred modality, the C5-related disease is at least one selected from a group consisting of PNH, aHUS, gMG, and NMO. In more preferred modalities, the C5-related disease is PNH. In certain respects, a pharmaceutical composition formulated for intravenous administration and comprising an anti-C5 antibody is administered prior to the first subcutaneous administration of the first phase. Preferably, the anti-C5 antibody in the intravenously administered composition is the same as the anti-C5 antibody in the subcutaneously administered composition. The intravenously administered pharmaceutical composition is the same as that described herein. In certain embodiments, the subcutaneous injection composition is administered subcutaneously on the same day as, or one or more days after, a dose of the intravenous injection composition is administered intravenously. One or more doses of the intravenous injection composition may be administered to a subject or patient before administering a first dose of the subcutaneous injection composition. In a preferred embodiment, the first dose of the subcutaneous injection composition is administered after the final dose of the intravenous injection composition. In certain formulations, the first subcutaneous administration of the first phase (Lcnnn / Lznz / E / YiAi) is given 0 days to 1 month after the final administration of the intravenously administered pharmaceutical composition. Specifically, the period between the first subcutaneous administration and the final intravenous administration is 0 days (i.e., within 24 hours), 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, or 31 days. In preferred modes, the period is 0 days (i.e., within 24 hours) to 14 days. In additional preferred modes, the period is 0 days (i.e., within 24 hours) to 10 days. In highly preferred modes, the period is 0 days (i.e., within 24 hours) to 8 days. III. A pharmaceutical composition for intravenous injection In certain aspects of the invention, the first subcutaneous administration in the first phase of the pharmaceutical composition for use of the present invention is administered after the final administration of a composition for intravenous administration. Therefore, in one embodiment of the present invention, a composition formulated for intravenous administration and comprising an anti-C5 antibody is administered intravenously prior to the first subcutaneous administration of the first phase. In a preferred embodiment, the anti-C5 antibody in the intravenous composition is the same as the anti-C5 antibody in the subcutaneous composition. Preferably, there is no intravenous administration after the first subcutaneous administration. Therefore, in an additional modality, the last intravenous administration is before the first subcutaneous administration. The pharmaceutical composition formulated for intravenous injection in the present invention is for use in the treatment or prevention of a C5-related disease, comprises an anti-C5 antibody, and is administered intravenously. The intravenous injection may be carried out using ordinary devices and methods for administering a pharmaceutical composition into a vein by injection. Such devices and methods specific to intravenous injection may also be selected. The anti-C5 antibody used for intravenous injection may be any antibody as described above for pharmaceutical compositions for subcutaneous injection. The pharmaceutical composition for intravenous injection and the pharmaceutical composition for subcutaneous injection may contain the same anti-C5 antibody or may contain different anti-C5 antibodies. In preferred embodiments, the anti-C5 antibody used for intravenous injection is the same antibody used for subcutaneous injection as described above. In certain embodiments, the pharmaceutical composition is administered intravenously at a dose of 50 to 5,000 mg of the antibody. An appropriate dose can be determined within a suitable range according to the condition of a subject or patient. If the pharmaceutical composition is administered intravenously to a subject repeatedly, the doses do not have to be the same each time and can be determined arbitrarily, provided they remain within the appropriate range. For example, the dose can be gradually reduced. In preferred embodiments, the dose range is 55 to 4,000 mg of the antibody. In further preferred embodiments, the dose range is 60 to 2,500 mg of the antibody. In most preferred embodiments, the dose range is 1,000 to 2,000 mg of the antibody. Preferred specific doses are 75 mg, 125 mg, 150 mg, 300 mg, 375 mg, 500 mg and 1,000 mg.Additional preferred doses are 375 mg, 500 mg, and 1,000 mg, and among these, the most preferred is 1,000 mg. In certain modalities, the number of times the pharmaceutical composition is administered by intravenous injection is not particularly limited and may be once or more times. In preferred modalities, the number of times is once, twice, or three times. In additional preferred modalities, the number of times is once or twice. In the most preferred modality, the number of times is once. Fewer administrations may reduce the burden or suffering of the patient. In certain modalities, if the pharmaceutical composition or Lcnnn / Lznz / E / YiAi is administered to a patient repeatedly, the appropriate administration time between doses is to be determined within a subject or composition is administered intravenously to a subject every 14 days.An interval for intravenous injections can be an appropriate interval for the administration conditions of a subject or specific between hours, 3 hours, 9 hours, in accordance with the The interval for intravenous injections is hours, 6 hours, hours, 12 hours, 13 hours, 18 hours, 19 hours, 24 hours, 25 hours, 30 hours, 31 hours, 36 hours, 37 hours, 42 hours, 43 hours, 2 hours, 8 hours, hours, 14 hours, 15 hours, 20 hours, 21 hours, 26 hours, 27 hours, 32 hours, 33 hours, 38 hours, 39 hours, 44 hours, 45 hours, a patient, injections 4 hours, 5 hours, 11 hours, 16 hours, 17 hours, 22 hours, 23 hours, 28 hours, 29 hours, 34 hours, 35 hours, 40 hours, 41 hours, 46 hours, 47 hours, 48 ​​hours, 3 days, days, 5 days, 6 days, 7 days, days, 9 days, 10 days, 11 days, 12 days, 13 days, or 14 days. In preferred modes, the dosing interval is from 24 hours to 10 days. In additional preferred modes, the dosing interval is from 48 hours to 7 days.In more preferred modalities, the administration interval is 3 to 5 days. In one embodiment, any pharmaceutically acceptable carrier available for a standard intravenous injection formulation may be included in the formulation. A carrier type used for intravenous injection may be appropriately selected from carriers generally known in the art. In certain embodiments, a pharmaceutical composition formulation may be any selected from the group consisting of liquid, semisolid, and solid. The solid composition is usually prepared by lyophilization from a liquid formulation. The lyophilized composition is usually reconstituted using water or saline solution only before intravenous injection. The formulation of the pharmaceutical composition for intravenous injection may be the same as or different from the formulation of the pharmaceutical composition for subcutaneous injection. In preferred embodiments, the formulation of the pharmaceutical composition for intravenous injection is the same as the formulation of the pharmaceutical composition for subcutaneous injection to lower manufacturing costs. When the composition is administered intravenously, a concentration of the anti-C5 antibody in a liquid formulation of the composition is determined within a standard range in the art. In one modality, a volume of the composition for intravenous injection is determined within a standard range in the art. In certain aspects, a dose of the intravenous injection composition is administered before an initial dose of another pharmaceutical composition is administered subcutaneously. The pharmaceutical composition for subcutaneous injection is the same as the one described above. In certain embodiments, the intravenous injection composition is administered intravenously on the same day as, or one or more days before, the first initial dose of the subcutaneous injection composition is administered subcutaneously. One or more doses of the intravenous injection composition may be administered to a subject or patient before administering an initial dose of the subcutaneous injection composition. In a preferred embodiment, the final dose of the intravenous injection composition is administered before the initial dose of the subcutaneous injection composition. q Lcnnn / Lznz / E / YiAi In certain formulations, the dose of the intravenous injection composition is administered on the same day or from 1 day to 1 month before the initial dose of the subcutaneous injection composition. The specific interval between the dose of the intravenous injection composition and the initial dose of the subcutaneous injection composition is 0 days (i.e., within 24 hours), 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, or 28 days. In preferred modes, the interval is 0 days (i.e., within 24 hours) to 14 days. In more preferred modes, the interval is 0 days (i.e., within 24 hours) to 0 days. In the most preferred modes, the interval is 0 days (i.e., within 24 hours) to 8 days. IV. Change of another pharmaceutical product In another aspect, the prior pharmaceutical compositions for subcutaneous or intravenous injection may be useful for the treatment or prevention of a C5-related disease in a subject who has been treated with at least one drug product for the treatment or prevention of the disease once or more. For example, the pharmaceutical compositions of the present invention may be useful for treating a patient who has a C5-related disease and has previously received treatment with at least one drug product for the treatment or prevention of the disease, but is expected to respond better to treatment with the pharmaceutical compositions of the present invention. In such cases, the medication may be changed from the drug product to the pharmaceutical composition of the present invention.In preferred embodiments, an initial dose of the intravenous injection composition of the present invention is administered after the final dose of the drug product that has been used in the prior treatment. In certain embodiments, the drug product comprises an active substance that is different from the anti-C5 antibody in the previous composition for subcutaneous and intravenous injection. In some embodiments, the active substance of the drug product is a C5 mRNA targeting siRNA, or an anti-C5 antibody that is different from the anti-C5 antibody comprising the previous composition for subcutaneous and intravenous injection. In preferred embodiments, the drug product comprises an antibody that is different from one of the antibodies in the previous composition for subcutaneous and intravenous injection. In the most preferred embodiment, the antibody comprising the drug product that was used in the previous treatment is eculizumab or its derivative Lcnnn / Lznz / E / YiAi. In certain embodiments, an initial dose of the intravenous injection composition of the present invention is administered on the same day as, or one or more days after, the final dose of the drug product is administered. The specific interval between the final dose of the drug product and the initial dose of the intravenous injection composition of the present invention is 0 days, meaning that the initial dose of the intravenous injection composition is administered on the same day as the final dose of the drug product; 1 day; 2 days; 3 days; 4 days; 5 days; 6 days; 7 days; 8 days; 9 days; 10 days; 11 days; 12 days; 13 days; 15 days; 16 days; 17 days; 18 days; 19 days; 20 days; or 21 days. In preferred embodiments, the intravenous injection composition of the present invention is administered 3 or more days after the final dose of the drug product.In more preferred embodiments, the intravenous injection composition of the present invention is administered 7 or more days after the final dose of the drug product. In further preferred embodiments, the intravenous injection composition of the present invention is administered 14 or more days after the final dose of the drug product. In even more preferred embodiments, the intravenous injection composition of the present invention is administered 21 or more days after the final dose of the drug product. V. A method of treatment or prevention In other respects, the invention covers methods for treating or preventing a C5-related disease. In one embodiment, the method comprises subcutaneously administering a pharmaceutical composition, which is formulated for subcutaneous or intravenous injection and comprises an anti-C5 antibody, wherein the composition is administered subcutaneously in two phases, wherein in both phases there is an interval between each two subcutaneous administrations, wherein each phase comprises at least one interval, and wherein in the first phase. i) at least one interval is shorter than at least one interval in the second phase, and ii) the antibody dose per administration is less than or the same as the antibody dose per administration in the second phase. The subcutaneously administered pharmaceutical composition is the same as that referred to above. In certain modalities, a pharmaceutical composition formulated for intravenous administration and comprising an anti-C5 antibody is administered prior to the first subcutaneous administration of the first phase. The intravenously administered pharmaceutical composition is the same as that referred to above. The conditions and diseases that are the target of a pharmaceutical composition for subcutaneous or intravenous injection used in the method are the same as those mentioned in the preceding sections II. A pharmaceutical composition for subcutaneous injection and III. A pharmaceutical composition for intravenous injection. VI. Vaccination Infectious diseases, such as meningococcal infections, can occur in a subject to whom the anti-C5 antibody has been administered. To prevent such infectious diseases, the subject can be immunized with a vaccine known to treat or prevent the diseases before, after, or when the aforementioned composition for subcutaneous and intravenous injection is administered. VII. Manufactured Article In another aspect of the invention, a manufactured article or product is provided that contains materials useful for the treatment or prevention of the C5-related diseases described above. The manufactured article or product comprises one or more containers and a label or package insert on or associated with the containers. Suitable containers include, for example, bottles, vials, syringes, SC solution syringes, etc. The containers may be formed from a variety of materials such as glass or plastic. The container holds a composition which, by itself or in combination with another composition, is effective in treating or preventing the condition and may have a sterile access port (for example, the container may be a vial having a stopper that can be pierced by a hypodermic injection needle). At least one active agent in the composition is an anti-C5 antibody described above.The label, package insert, or such document indicates that the composition is used to treat the condition of choice, e.g., any of the C5-related diseases as described above. In certain embodiments, the composition contained in the container of the manufactured article or product is formulated for subcutaneous injection. The manufactured article or product in this embodiment of the invention may further comprise a package insert indicating the following method of administration. The pharmaceutical composition is administered subcutaneously in two phases, wherein in both phases there is an interval between each two subcutaneous administrations. Each phase comprises at least one interval. In the first phase, i) at least one interval is shorter than at least one interval in the second phase, and ii) the antibody dose per administration is lower than the antibody dose per administration in the second phase. o Lcnnn / Lznz / E / YiAi In certain embodiments, the manufactured article or product may further comprise an additional container with a composition contained herein, wherein the composition comprises an additional therapeutic agent. The manufactured article in this embodiment may further comprise a package insert indicating that the compositions can be used to treat a particular condition. Alternatively, or additionally, the manufactured article may further comprise another additional container comprising a pharmaceutically acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution, and dextrone solution. It may further include other commercially and user-desirable materials, including other buffers, diluents, fibers, needles, and syringes. EXAMPLES The following are examples of methods and compositions of the invention. It is understood that there are various other embodiments that can be implemented, given the preceding general description. Example 1 Generation of an anti-C5 antibody The anti-C5 antibody 305LO15 in WO2016 / 098356 was prepared by an ordinary method. Briefly, the genes encoding the heavy chain variable (HV) domain of 305LO15 were combined with the genes encoding a human IgG1 heavy chain constant (CH) domain variant SG115 (SEC. ID NO.: 13). The genes encoding the light chain variable (LV) domain of 305LO15 were combined with the genes encoding a human light chain constant (CL) domain (SKI, SEC. ID NO.: 18). The antibodies were expressed in HEK293 cells co-transfected with the combination of light and heavy chain expression vectors and purified by protein A. Example 2 Protein-based drugs, such as antibody drugs, are typically administered intravenously because proteins are difficult to concentrate. In fact, eculizumab, the only currently approved antibody available for treatment, is administered intravenously. If subcutaneous injection becomes available, it will reduce the patient burden, such as the need for outpatient treatment and the length of time spent in the hospital for intravenous injections, since self-injection is possible. To examine the possibility of subcutaneous administration of the anti-C5 antibody, 305LO15, described in WO2016 / 098356, was selected because of its high solubility. It is thought that this high solubility allows the protein pharmacist to be administered in a smaller volume, thus permitting subcutaneous injection. The pharmaceutical compositions for intravenous injection and subcutaneous injection were prepared by being the following general formulation. 170 mg / mL 305LO15 mM of histidine / aspartic acid 100 mM arginine hydrochloride 0.05% Poloxamer 188 pH 5.8 To compare the pharmacokinetics of 305LO15 after subcutaneous or intravenous injection, cynomegos were divided into two groups: a subcutaneous injection group and an intravenous injection group. 305LO15 was administered subcutaneously to the animals in the first group (three males and three females) once a week for a total of 22 doses at 40 mg / kg of antibody per dose. Plasma concentrations of 305LO15 in these animals were measured using ELISA assays at the time points shown in Figure 1A. 305LO15 was administered intravenously to the animals in the second group (six males and six females) once a week for a total of five doses at 40 mg / kg of antibody per dose. A concentration of 305LO15 in plasma of the q Lcnnn / Lznz / E / YiAi animals was measured by ELISA analysis at the time points shown in Figure IB. As shown in Figure 1A, the plasma concentration of 305LO15 in cynomologist monkeys increased following subcutaneous injections, confirming that 305LO15 can be administered by subcutaneous injection as therapy. The ratio of the initial increase in plasma concentration after the initial dose was lower with subcutaneous administration (Figure 1A) than with intravenous injection (Figure 1B). Example 3 Next, it was investigated whether the relatively low rate of increase in plasma concentration after the initial subcutaneous injection dose could be offset by an intravenous injection of 305LO15. Five male and five female cynomologist monkeys received an initial intravenous dose of 305LO15 at a concentration of 100 mg / kg of antibody. One week after the initial intravenous administration, subcutaneous injection of 305LO15 was initiated. A total of 26 subcutaneous injections were administered, once weekly at a concentration of 40 mg / kg of antibody per dose. As shown in Figure 2, the rate of increase in plasma concentration of 305LO15 was faster when the initial antibody dose was administered as an intravenous injection followed by maintenance doses via subcutaneous injection than when no initial intravenous dose was given. The plasma concentration of 305LO15 was reached and maintained at a level comparable to that shown in Figure 1A. This faster increase in plasma concentration of 305LO15 is thought to contribute to a more rapid onset of the drug's therapeutic effect. Example 4 To stimulate effective plasma concentrations of 305LO15, the ratio of free antigen (C5) plasma concentration or complement activity to antibody (305LO15) plasma concentration was determined in cynomogenetic monkeys. 305LO15 was administered intravenously (0.8 mg / kg, 4 mg / kg, or 20 mg / kg) or subcutaneously (4 mg / kg). Antibody and free C5 plasma concentrations were measured by ELISA. Complement activity was measured by red blood cell hemolytic assay. As shown in Figures 3A-3B, the concentration of free C5 was suppressed to a level of less than sub-microg / mL when the plasma concentration of 305LO15 was maintained above 40 microg / mL of 305LO15 (Figure 3A), and 40 microg / mL or higher plasma concentration of 305LO15 inhibits complement activity (hemolysis) to less than 20% of the reference value (i.e., no antibody applied) (Figure 3B).It is estimated that complement activity is suppressed to less than 20% of the reference value (i.e., no antibody is injected) when 40 micro g / mL or higher concentrations of 305LO15 are maintained in the plasma. Example 5 To determine the appropriate dosages and administrations for 305LO15 to maintain effective plasma concentrations for clinical trials, the time course of plasma concentrations in humans was predicted by simulation. First, plasma concentrations of 305LO15 were measured over time after the antibody was administered to cynomologist monkeys at 0.8, 4, and 20 mg / kg of antibody for each dosage. Cynomologist monkey PK parameters were estimated by analyzing the data using a two-compartment model. Using allometric scaling, human PK parameters were estimated based on the cynomologist monkey PK parameters.The estimated human PK parameters are shown in Table 1 (parameter abbreviations in Table 1: BW, body weight; CL, total drug separation; F, bioavailability, or a fraction of an administered dose of a drug that becomes systemically available; Ka, absorption rate constant; mAb, monoclonal antibody; PK, pharmacokinetics; Q, intercompartmental separation; SC, subcutaneous; Ve, volume of distribution for the central compartment; V, volume of distribution for the peripheral compartment). o Lcnnn / Lznz / E / YiAi Table 1 or Lennn / Lznz / E / YiAi IT <N CO vCQ CC CN The human pharmacokinetic profile was estimated for each group expected for the phase 1 / 2 study (Figures 4A-4C). Part 1 of the study was designed to include three groups of subjects. The first group consists of subjects who receive 305LO15 intravenously once at a dose of 75 mg / body. The second group consists of subjects who receive 305LO15 intravenously once at a dose of 150 mg / body. The third group consists of subjects who receive 305LO15 subcutaneously once at a dose of 170 mg / body. It is predicted that the plasma concentration of 305LO15 in subjects who did not receive one of the above doses will not be maintained above the threshold (40 µg / mL) for more than one week (Figure 4A). Part 2 of the study was designed to include a group of subjects to whom 305LO15 was administered intravenously three times (initially at a dose of 300 mg / body, then at 500 mg / body one week after the initial administration, and finally at 1000 mg / body two weeks after the second administration) and, beginning two weeks after the final intravenous administration, 305LO15 was administered subcutaneously once a week at a dose of 170 mg / body. It is inferred that the concentration of 305LO15 is maintained above the PD threshold (40 µg / mL) by the dosing regimen for the Part 2 study (Figure 4B). Part 3 of the study was designed to include three groups of subjects. 305LO15 was initially administered intravenously to subjects in all groups once at a dose of 500 mg / body. Starting the day after the initial administration, 305LO15 was administered subcutaneously to subjects in the first group once weekly at a dose of 170 mg / body, to subjects in the second group once every two weeks at a dose of 340 mg / body, and to subjects in the third group once every four weeks at a dose of 600 mg / body. The concentration of 305LO15 was predicted to remain above the PD threshold (40 µg / mL) in all three groups in Part 3 of the study (Figure 4C). Example 6 Eculizumab has been used to treat patients with NHP or aHUS. If 305LO15 is expected to have a more desirable effect than eculizumab in a patient with NHP or aHUS, the patient's drug therapy may be switched from eculizumab to 305LO15. However, there is a possibility that 305LO15 may form immune complexes with C5 and eculizumab within the body because the epitope of 305LO15 is different from that of eculizumab; that is, 305LO15 binds to the beta chain of C5, while eculizumab binds to the alpha chain of C5. The formation of such an immune complex can cause abnormal activation and is therefore undesirable and should be avoided as much as possible. o Lcnnn / Lznz / E / YiAi To investigate whether 305LO15 forms an immune complex with eculizumab (ECZ, heavy chain sequence shown in SEC. ID NO.: 19 and light chain sequence shown in SEC. ID NO.: 20) and human cholinesterase O5 (hC5, SEC. ID NO.: 21), in vitro analysis was performed using size exclusion chromatography (SEC). hC5 was prepared according to the method described in WO2016 / 098356. ECZ, hC5, and 305LO15 were dialyzed against DPBS pH 7.4 for buffer exchange. ECZ and hC5 were then mixed and incubated at 37°C for 3–4 hours. After incubation, 305LO15 was added to this mixture containing ECZ and hC5. The final concentration of ECZ and hC5 was adjusted to 200 µg / mL, and the concentration of 305LO15 was adjusted to 0, 25, 125, 250, or 1250 µg / mL. After incubating these mixtures at 37°C for 3–4 hours, the SEC assay was performed at pH 7.4 and pH 6.0. The specific SEC conditions were as identified below. HPLC System: Waters Alliance e2695 HPLC System Column: TSKgel G4000SWXL Column temperature: 25°C Eluent: 50 roM Na-PB / 300 mM NaCl, pH 7.4 or pH 6.0 Flow rate: 0.5 mL / min Detection: UV absorption 220 nm Injection: 10 micro L As a result, 305LO15 at concentrations of 125 to 1250 µg / mL does not affect the SEC profile at pH 6.0, but it does affect the profile at pH 7.4. More specifically, when 305LO15 is mixed with ECZ and hC5, the peaks of the large ECZ / hC5 / 305LO15 immune complexes, which were not detected at pH 6.0, were detected at pH 7.4 (see the peaks indicated by the arrows in Figure 5, top), in addition to the peaks of the small complexes (see peaks '2Ag+Ab' and 'Ag+Ab' in Figure 5, top). Only the peaks of the small complexes were detected at pH 6.0 (see the peaks in Figure 5, bottom, which correspond to '2Ag+Ab' and 'Ag+Ab' in Figure 5, top). This means that 305LO15 binds to the ECZ / hC5 complex at pH 7.4, but not at pH 6.0, in accordance with the binding characteristics of 305LO15 (which binds to hC5 at pH 7.4 but not at pH 6.0).Based on these results, it is suggested that simultaneous administration of 305LO15 and ECZ to a subject could result in the formation of large immune complexes in plasma. Example 7 The BP39144 study, an adaptive phase I / II study, evaluates the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of 305LO15 in healthy volunteers and in patients with paroxysmal nocturnal hemoglobinuria (PNH). Part 1 of Study BP39144 (a parallel, placebo-controlled, adaptive, subject / investigator-shielded, randomized, cluster- or Lcnnn / Lznz / E / YiAi study) evaluated the safety and tolerability of a single dose of 305LO15 in healthy volunteers. At each group / dose level, a total of 5 healthy volunteers were randomized to receive a single intravenous (IV; Groups 1 and 2) or subcutaneous (SC; Group 3) administration of either 305LO15 or placebo. The study has an adaptive design, with ongoing assessment of safety, tolerability, pharmacokinetics (PK), and drug-predominant (DP) data available prior to the initiation of the next administration. The planned dosage levels for Groups 1, 2, and 3 were 75 mg IV, 150 mg IV, and 170 mg SC, respectively (Figure 4A). Based on the preliminary review of PK and PD data from Group 1, the doses for Groups 2 and 4 were reduced to 125 mg IV (Group 2) and 100 mg SC (Group 3). For IV infusion, blood samples were collected pre-dose, at the end of the IV infusion (1 hour), 2, 6, 12, 24, 48, 72, 96, and 144 hours post-dose, and on days 14, 21, 28, 35, 42, 56, 84, and 91. For SC administration, blood samples were collected pre-dose, at 12, 24, 48, 72, 96, and 144 hours post-dose, and on days 14, 21, 28, 35, 42, 56, 84, and 91. The preliminary results of Part 1 of Study BP39144 indicate that 305LO15 was well tolerated at all dose levels evaluated (75 and 125 mg IV and 100 mg SC). Available clinical safety data did not reveal any significant safety concerns and showed no evidence to suggest a pattern of adverse events or laboratory test abnormalities. There were no notable findings or trends in vital signs or 12-lead electrocardiograms in either treatment group. Preliminary serum PK results and simulated time-concentration profiles for 305LO15 are presented in Figures 6, 7, and 8. Based on these data, the PK of 305LO15 in healthy subjects was in line with initial human PK predictions based on cynomologist monkey PK data (Example 5). Following IV dosing, exposure appeared to be dose-proportional from 75 to 125 mg. The terminal half-life (ti / 2) for a typical 70 kg patient was estimated to be approximately 25 days. Following SC administration, preliminary PK results showed that 305LO15 exposure peaked at approximately day 7, and bioavailability was approximately 90%. After absorption, the ti / 2 was comparable to the ti / 2 following IV infusion. The preliminary assessment of the response-exposure relationship supported the initial prediction, i.e., approximately 40 micro g 305LO15 per mL of blood is required to achieve complete inhibition of complement (Figure 9). Example 8 Part 2 of Study BP39144 (a global, multicenter, multi-dose, open-label, intra-individual dose-escalation study) evaluated the safety and tolerability over a total duration of 5 months, and the pharmacodynamic effect of multiple doses of 305LO15 on complement activity in the treatment of previously untreated patients with non-Hodgkin's pyelonephritis (NHP). Six patients with NHP were enrolled in this study. Enrolled patients were either not previously treated with any complement inhibitor or had been previously treated but discontinued treatment due to lack of efficacy based on a heterozygous C5 missense mutation, and showed elevated serum LDH levels (>1.5 x ULN) at screening (ULN: upper limit of normal). One patient (patient X) among six patients was a patient with PNH and a candidate for complement inhibitor therapy. Patient X received three ascending single IV doses: a single infusion of 375 mg of 305LO15 on day 1, followed by a single infusion of 500 mg of 305LO15 on day 8, and further followed by a single infusion of 1000 mg of 305LO15 on day 22. The first SC administration (170 mg) was initiated on day 36, followed by weekly SC (CS) injections (170 mg) of 305LO15, which will be continued for the total treatment duration of 5 months. The preliminary pharmacodynamic results for Patient X are shown in Table 2 and Figures 10A-10B. LDH levels, as a pharmacodynamic marker of hemolysis, fell to levels within the normal range by day 15, fell further by day 36, and remained at the normalized level by day 43 (Table 2 and Figure 10A). As shown in Table 2 and Figure 10B, liposome immunoassay (LIA) results showed that complement activity was completely inhibited at the end of the infusion on the study start day, day 1. The 375 mg dose of 305LO15 on day 1 maintained complete complement inhibition until the next 500 mg dose of 305LO15 on day 8. The 500 mg dose of 305LO15 on day 8 maintained complete complement inhibition until the next 1000 mg dose of 305LO15 on day 22.The 1000 mg dose of 305LO15 on day 22 maintains complete complement inhibition until the next SC dose of 170 mg of 305LO15 on day 36. The SC dose on day 36 maintains complete complement inhibition on day 43. The 305LO15 was well tolerated with only mild abdominal pain or Lcnnn / Lznz / E / YiAi unrelated to the treatment. o Lcnnn / Lznz / E / YiAi Table 2 LDH [U / mL] LIA [U / mL] Day 1 pre-dose 2216 80 Day 1 post-dose Not collected Complete Inhibition Day 2 2217 Complete Inhibition Day 5 762 Complete Inhibition Day 8 pre-dose 824 Complete Inhibition Day 8 post-dose 634 Complete Inhibition Day 9 Complete Inhibition Day 15 474 Complete Inhibition Day 22 455 Complete Inhibition Day 36 414 Complete Inhibition Day 43 461 Complete Inhibition Example 9 Part 3 of the BP39144 Study (a global, multicenter, multidose, open-label study) evaluates the safety and tolerability over a total duration of 5 months, and the pharmacodynamic effect of multiple doses of 305LO15 on complement activity in patients with non-Hodgkin's pyelonephritis (NHP) currently treated with eculizumab. Eighteen patients with NHP are being enrolled in this study. Enrolled patients have been continuously treated with eculizumab for at least 3 months prior to trial enrollment and have received regular eculizumab infusions. One patient (patient Y) among 18 patients was a patient with PNH treated with eculizumab, where eculizumab was finally administered 14 days before the first IV infusion of 305LO15. Patient Y received a single IV loading dose; a single infusion of 1000 mg of 305LO15 on day 1. The first SC administration (680 mg) was provided on day 8, followed by SC injections every 4 (C4W) (680 mg) of 305LO15 which will be continued for a total treatment duration of 5 months. Preliminary pharmacodynamic results from Patient Y are shown in Table 3. LDH levels, as a pharmacodynamic marker of hemolysis, remained within the reference range from the first dose on day 43 (Table 3). As shown in Table 3, liposome immunoassay (LIA) results indicate that complement activity was completely inhibited at the end of the infusion on the study's baseline day, day 1. The 1000 mg dose of 305LO15 on day 1 maintained complete complement inhibition until the 680 mg subcutaneous dose of 305LO15 on day 8. The subcutaneous dose on day 8 maintained complete complement inhibition on day 43. q Lcnnn / Lznz / E / YiAi Table 3 LDH [U / mL] (103-229) LIA [U / mL] Day -1 328 Complete Inhibition Day 1 pre-dose 315 Complete Inhibition Day 1 post-dose 10-12 h 421 - Day 2 273 Complete Inhibition Day 8 pre-dose 271 Complete Inhibition Day 14 336 Complete Inhibition Day 22 274 Complete Inhibition Day 29 - Complete Inhibition Day 36 338 Complete Inhibition Day 43 344 Complete Inhibition Example 10 Dose-Regimen Findings in Patients with PNPI This is a global, multicenter, multidose, open-label study in patients with non-Hodgkin's disease (NHD) treated with eculizumab (see also Example 9). Approximately eighteen adult male and female NHD patients were enrolled and treated with eculizumab. The objective of Part 3 is to determine the optimal dosing regimen with a low treatment load for these patients. Each dosing regimen studied helps achieve exposure that inhibits activation of the entire terminal pathway through the total dosing period. Target exposure was defined based on PK, PD, and efficacy data from Part 2. For all patients in Part 3, dosing with 305LO15 was initiated no later than two weeks after the patient's last dose of eculizumab. An IV loading dose was followed by a subcutaneous maintenance dose. During Part 3, a portion of the original subcutaneous (SC) dosing regimen was altered for additional safety enhancement. Three different SC dosing regimens (including weekly [CS], biweekly [C2S], or monthly [C1M] dosing of 305 µL / L) were evaluated (see Figure 11). Patients in Arm A were randomly assigned to receive the SC dosing of 170 mg CS eight times in Phase 1. With the ninth SC dose (study day 64), which is the first administration in Phase 2, patients in Arm A began the C4S maintenance regimen of 680 mg. The IV loading dose was administered, for example, approximately 24 hours prior to the first SC dose for some patients. In Part 3, patients received treatment for up to five months. Should a patient experience signs and symptoms of their underlying disease, such as advanced hemolysis, which may be due to an acute event such as acute illness, trauma, or surgery, etc.One or more additional IV doses of 305LO15 may be administered. Prior to this IV dose, an unscheduled PD biomarker sample should be taken to evaluate the underlying cause of advanced hemolysis. q Lcnnn / Lznz / E / YiAi The preliminary pharmacodynamic results for patients Z1 and Z2 in Arm A are shown in Table 4. LDH levels, as a pharmacodynamic marker of hemolysis, remained at baseline levels from the first dose on day 106 (Table 4). As shown in Table 4, liposome immunoassay (LIA) results demonstrated that complement activity was completely inhibited at the end of the infusion on the study's baseline day, day 1. The 1000 mg dose of 305LO15 on day 1 maintained complete complement inhibition until the first subcutaneous (SC) dose of 170 mg of 305LO15 on day 8. Following the 9th SC dose (study day 64), those patients who had received the C4S maintenance regimen of 680 mg were treated. Complete complement inhibition (LIA [U / mL] < 10) in Z2 patients has been maintained during SC dosing (day 64 to day 106).Complement inhibition in Patient Z1 has been completely or sufficiently inhibited during SC dosing (day 64 to day 106). The regimen in arm A has been well tolerated with only mild side effects (shoulder paresthesia in patients Z1, common in patients Z2) unrelated to treatment. Table 4 Patient Z1 Patient Z2 LDH [U / mL] LIA [U / mL] LDH [U / mL] LIA [U / mL] Day 1 433 < 10 305 < 10 Day 1 pre-dose 408 < 10 313 12 Day 1 post-dose - < 10 - < 10 Day 2 367 < 10 253 < 10 Day 8 pre-dose 370 < 10 248 < 10 Day 15 365 < 10 293 < 10 Day 22 431 < 10 313 < 10 Day 29 408 11 316 < 10 Day 36 428 < 10 307 < 10 Day 43 473 < 10 333 < 10 Day 64 435 < 10,343 < 10 Day 78,445 11,329 < 10 Day 92,419 11,272 < 10 Day 106,448 < 10 305 < 10 Example 11 Open Label Extension (OLE) in Patients with PNH This is in OLE for patients who participated in Part 3 and who benefited from treatment with 305LO15. The number of patients enrolled does not exceed the number enrolled in Part 3 of the Example 10 study. Patients transitioning from Part 3 of the study initially remain on the same subcutaneous (SC) dosing regimen they received in Part 3. Depending on emerging safety, pharmacokinetic, and pharmacodynamic (PK) data from Part 3 of the study, the SC dosing regimen for patients enrolled in the OLE is therefore adjusted. The duration of treatment is up to a maximum of two years of OLE enrollment. It is hereby stated that, as of this date, the best method known to the applicant for putting the aforementioned invention into practice is the one that is clear from the present description of the invention.

Claims

CLAIMS Having described the invention as above, the following claims are claimed as property:

1. A pharmaceutical composition for use in a method of treating or preventing a C5-related disease, which is formulated for subcutaneous injection, and comprises an anti-C5 antibody, wherein the composition is administered subcutaneously in two phases, wherein in both phases there is an interval between each two subcutaneous administrations, wherein each phase comprises at least one interval, wherein in the first phase i) at least one interval is shorter than at least one interval in the second phase, and ii) the dose of the antibody per administration is lower than or equal to the dose of the antibody per administration in the second phase.

2. The pharmaceutical composition for use according to claim 1, wherein at least one interval in the first phase is from 1 day to 2 months.

3. The pharmaceutical composition for use according to claim 1 or 2, wherein at least one interval in the first phase is from 5 days to 14 days.

4. The pharmaceutical composition for use in accordance with any of claims 1 to 3, wherein at least one interval in the second phase is from 2 days to 6 months.

5. The pharmaceutical composition for use in accordance with any of claims 1 to 4, wherein at least one interval in the second phase is from 15 days to 3 months.

6. The pharmaceutical composition for use in accordance with any of claims 1 to 5, wherein the dose of the antibody in the first-phase subcutaneous administration is from 50 mg to 350 mg.

7. The pharmaceutical composition for use according to any of claims 1 to 6, wherein the antibody dose for subcutaneous administration in the first phase is 150 mg to 200 mg and lower than the subcutaneous administration dose in the second phase, preferably wherein the antibody dose in the first phase is 170 mg.

8. The pharmaceutical composition for use according to any of claims 1 to 6, wherein the antibody dose for subcutaneous administration in the first phase is 300 mg to 350 mg and is the same as the antibody dose for subcutaneous administration in the second phase.

9. The pharmaceutical composition for use of oi cnnn / ι ζπζ / β / υιλι 87 in accordance with any of claims 1 to 8, wherein the number of subcutaneous administrations in the first phase is from 1 to 12.

10. The pharmaceutical composition for use according to claim 1 to 9, the number of subcutaneous administrations in the first phase is from 5 to 10, preferably where the number is 8.

11. The pharmaceutical composition for use according to any of claims 1 to 10, wherein the dose of the antibody per administration in the second phase is 350 to 1,000 mg or 650 to 700 mg.

12. The pharmaceutical composition for use according to any of claims 1 to 7 and 9 to 11, wherein the dose of anti-C5 antibody for administration in the first phase is three to five times lower than the dose of anti-C5 antibody for administration in the second phase.

13. The pharmaceutical composition for use according to any of claims 1 to 12, wherein a pharmaceutical composition formulated for intravenous administration and comprising an anti-C5 antibody is administered intravenously prior to the first subcutaneous administration of the first phase.

14. The pharmaceutical composition for use according to claim 13, wherein the first subcutaneous administration of the first phase is administered 0 days to 1 month after the final administration of the pharmaceutical composition.

15. The pharmaceutical composition for use according to claim 13 or 14, wherein the antibody dose for intravenous administration is from 100 to 2,000 mg.

16. The pharmaceutical composition for use according to any one of claims 1 to 15, wherein the C5-related disease is any one selected from a group consisting of rheumatoid arthritis (RA); lupus nephritis; ischemia-reperfusion injury; paroxysmal nocturnal hemoglobinuria (PNH); atypical hemolytic uremic syndrome (aHUS); dense deposit disease (DDD); macular degeneration; hemolysis, elevated liver enzymes, and low platelet syndrome (HELLP); thrombotic thrombocytopenic purpura (TTP); spontaneous fetal loss; pauci-immune vasculitis; epidermolysis bullosa; recurrent fetal loss; multiple sclerosis (MS); traumatic brain injury; and injury resulting from myocardial infarction, cardiopulmonary bypass, or hemodialysis.

17. A method for treating or preventing a C5-related disease, characterized in that it comprises subcutaneous administration to a subject of a pharmaceutical composition, which is formulated for subcutaneous injection comprising an anti-C5 antibody, wherein the composition is administered subcutaneously in two phases, wherein in both phases there is an interval between each two subcutaneous administrations, wherein each phase comprises at least one interval, and wherein in the first phase, i) at least one interval is shorter than at least one interval in the second phase, and ii) the dose of the antibody per administration is lower than or the same as the dose of the antibody per administration in the second phase.

18. Use of an anti-C5 antibody in the manufacture of a pharmaceutical composition to treat or prevent a C5-related disease, wherein the composition is formulated for subcutaneous injection, comprises the anti-C5 antibody, and wherein the composition is administered subcutaneously in two phases, wherein in both phases there is an interval between each two subcutaneous administrations, wherein each phase comprises at least one interval, and wherein in the first phase, i) at least one interval is shorter than at least one interval in the second phase, and ii) the dose of the antibody per administration is less than or the same as the dose of antibody per administration in the second phase.

19. A product for treating or preventing a C5-related disease, characterized in that it comprises (a) a container; (b) a pharmaceutical composition in the container, wherein the pharmaceutical composition is formulated for subcutaneous injection and comprises an anti-C5 antibody; and (c) a document instructing that the pharmaceutical composition is administered subcutaneously in two phases, wherein in both phases there is an interval between each two subcutaneous administrations, wherein the phase comprises at least one interval and wherein in the first phase i) at least one interval is shorter than at least one interval in the second phase, and ii) the dose of the antibody per administration is lower than or equal to the antibody for administration in the second phase.