Anti-c5 antibodies and methods of use

Abstract

[Problem to be Solved] The object of this invention is to provide an anti-C5 antibody and a method of using it. [Means to Solve the Problem] This invention provides an anti-C5 antibody and a method of using it. In some embodiments, the isolated anti-C5 antibody of this invention binds to the antigenic determinant within the β chain of C5 with higher affinity at neutral pH than at acidic pH. This invention also provides an isolated nucleic acid encoding the anti-C5 antibody of this invention. This invention also provides a host cell comprising the nucleic acid of this invention. This invention also provides a method for manufacturing an antibody, comprising culturing the host cell of this invention to manufacture the antibody. This invention further provides a method for manufacturing an anti-C5 antibody, comprising immunizing an animal with a polypeptide comprising the MG1-MG2 domains of the β chain of C5. The anti-C5 antibody of this invention can be used as a drug.

Description

Anti-C5 antibody and its usage This invention relates to anti-C5 antibodies and their methods of use. The complement system plays a crucial role in the clearance of immune complexes and in immune responses against vectors, foreign antigens, virus-infected cells, and tumor cells. Approximately 25 to 30 complement proteins have been identified as a complex collection of plasma proteins and membrane cofactors. Complement components achieve their immune defense functions through a series of complex enzymatic cleavage and membrane-binding reactions, resulting in a complement cascade that leads to the production of products with opsonic, immunomodulatory, and cytolytic functions. Currently, it is generally accepted that the complement system can be activated via three different pathways: the classical pathway, the lectin pathway, and the alternative pathway. These pathways share many complement components, and although they differ in their initiation steps, 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. Independently, the first step in activating the lectin pathway is the binding of specific lectins, such as mannan-binding lectin (MBL), H-ficolin, M-ficolin, L-ficolin, and C-type lectin CL-11. In contrast, the alternative pathway spontaneously undergoes a low degree of turnover activation, which can readily expand on foreign or other abnormal surfaces (bacteria, yeast, virus-infected cells, or damaged tissue). These pathways converge at the site where complement component C3 is cleaved by active proteolytic enzymes to produce C3a and C3b. C3a is an anaphylatoxin. C3b binds to bacteria and other cells, as well as specific viruses and immune complexes, and tags them for removal from circulation (the role of opsonins is known). C3b also forms complexes with other components to form C5 convertase, which cleaves C5 into C5a and C5b. C5 is a 190 kDa protein found in normal serum at a concentration of approximately 80 μg / ml (0.4 μM). C5 is glycosylated, with approximately 1.5% to 3% of its mass being sugar. Mature C5 is a heterodimer consisting of a 115 kDa α-chain linked by disulfide bonds to a 75 kDa β-chain. C5 is synthesized as a single-chain precursor protein of 1676 amino acids (pro-C5 precursor) (see, for example, Patent Documents 1 and 2). The pro-C5 precursor is cleaved to produce a β-chain as an amino-terminal fragment and an α-chain as a carboxyl-terminal fragment. The α-chain and β-chain polypeptide fragments are linked together by disulfide bonds to form the mature C5 protein. When the complement pathway is activated, the mature C5 cell is cleaved into C5a and C5b fragments. C5a is cleaved from the α chain of C5 by C5 convertase as an amino-terminal fragment, comprising the first 74 amino acids of the α chain. The remaining portion of the mature C5 cell is fragment C5b, which contains the remaining α chain bonded to the β chain by disulfide bonds. Approximately 20% of the 11 kDa mass of C5a is sugar. C5a is another anaphylatoxin. C5b combines with C6, C7, C8, and C9 to form a membrane attack complex (MAC, C5b-9, terminal complement complex (TCC)) on the surface of target cells. When a sufficient amount of MAC inserts into the target cell membrane, MAC pores are formed to regulate rapid permeability and cytolysis of the target cell. As mentioned above, C3a and C5a are anaphylatoxins that can trigger mast cell degranulation, releasing histamine and other mediators of inflammatory responses, resulting in smooth muscle contraction, increased vascular permeability, leukocyte activation, and other inflammatory phenomena, including hypercellularity due to cell proliferation. C5a can also act as a chemotactic peptide, attracting granulocytes, such as neutrophils, eosinophils, basophils, and monocytes, to complement activation sites. The activity of C5a is regulated by the plasma enzyme carboxypeptidase N, which removes arginine from the carboxyl terminus of C5a to form C5a-des-arginine (C5a-des-Arg) derivatives. C5a-des-arginine exhibits only 1% anaphylatoxin activity and polymorphonuclear kinetic activity of unmodified C5a. While a properly functioning complement system provides robust defense against infectious microorganisms, improper regulation or activation of complement has been implicated in the pathogenicity of a variety of diseases, 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)); hemolytic, elevated liver enzymes and low platelet count (HELLP) syndrome; thrombotic thrombocytopenic purpura (TTP); spontaneous abortion; pauci-immune vasculitis; epidermal bullous lysis; recurrent miscarriage; multiple sclerosis (MS); traumatic brain injury; and damage caused by myocardial infarction, cardiopulmonary bypass, and hemodialysis (see, for example, Non-Patent Literature 1). Therefore, inhibiting excessive or uncontrolled activation of the complement cascade can provide clinical benefits to patients with these conditions. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder in which erythrocytes are compromised and destroyed more rapidly than normal erythrocytes. PNH originates from the clonal proliferation of hematopoietic stem cells with a somatic mutation in the PIG-A (phosphatidylinositol glycan class A) gene, located on the X chromosome. The PIG-A mutation initially inhibits the synthesis of glycosylphosphatidylinositol (GPI), a molecule required for many proteins to anchor to the cell surface. Therefore, PNH hemoglobin cells lack GPI-anchoring proteins, including the complement regulatory proteins CD55 and CD59. Under normal conditions, these complement regulatory proteins prevent MAC formation on the cell surface, thus preventing erythrocyte lysis. The absence of GPI-anchoring proteins leads to a complement-regulated hemolytic response in PNH. PNH is characterized by hemolytic anemia (a decrease in the number of red blood cells), hemeuria (the presence of hemoglobin in the urine, especially after sleep), and hemeemia (the presence of hemoglobin in the blood). Individuals with PNH are known to experience paroxysmal episodes, defined in this article as the incidence of black urine. Hemolytic anemia is attributed to the intravascular destruction of red blood cells by complement components. Other known symptoms include dysphagia, fatigue, erectile dysfunction, thrombosis, and recurrent abdominal pain. Eculizumab is a human monoclonal antibody targeting complement protein C5 and is the first approved treatment for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) (see, for example, Non-Patent Literature 2). Eculizumab inhibits C5 convertase from cleaving C5 into C5a and C5b, preventing the formation of the terminal complement complex C5b-9. Both C5a and C5b-9 lead to terminal complement regulation, which is characteristic of PNH and aHUS (see also Patent Literature 3, Patent Literature 4, Patent Literature 5, and Patent Literature 6). Numerous reports have described anti-C5 antibodies. For example, Patent Document 7 describes an anti-C5 antibody that binds to the α chain of C5 but not to C5a, and prevents C5 activation. Patent Document 8 describes an anti-C5 monoclonal antibody that inhibits the formation of C5a. On the other hand, Patent Document 9 describes an anti-C5 antibody that recognizes the proteolytic site of C5 convertase on the α chain of C5 and inhibits the conversion of C5 to C5a and C5b. Patent Document 10 describes an anti-C5 antibody having at least 1 x 10 7 M -1 The affinity constant. Antibodies (IgGs) bind to nascent Fc receptors (FcRn) and exhibit a long plasma retention time. IgG binding to FcRn is typically observed in acidic environments (e.g., pH 6.0) and rarely in neutral environments (e.g., pH 7.4). Generally, IgGs are incorporated into cells nonspecifically via endocytosis and return to the cell surface via endosomal FcRn binding in the acidic environment of the endosome. Subsequently, IgGs dissociate from the FcRn in the neutral environment of the plasma. Unbound IgGs are broken down in lysosomes. When the FcRn binding capacity of IgG in acidic environments is eliminated by introducing a mutation into its Fc region, IgG will not recirculate from the endosome into the plasma, resulting in significantly impaired plasma retention of IgG. To improve plasma retention of IgGs, a method to increase their binding to FcRn in an acidic environment has been reported. When the FcRn binding capacity of IgG in an acidic environment is enhanced by introducing a monoamino acid to replace its Fc region, IgG is more efficiently recirculated from the endosome into the plasma, thus showing improved plasma retention. Meanwhile, there have also been reports indicating that IgG with enhanced FcRn binding in a neutral environment does not dissociate from FcRn in neutral plasma, and even when it returns to the cell surface by binding to FcRn in an acidic environment, its plasma retention remains unchanged, or rather, is worse (see, for example, Non-Patent Literature 3; Non-Patent Literature 4; Non-Patent Literature 5). Recently, antibodies that bind to antigens in a pH-dependent manner have been reported (see, for example, Patent Documents 11 and 12). These antibodies bind strongly to antigens in a neutral plasma environment and dissociate from antigens in an acidic intracellular environment. After dissociation from antigens, the antibodies become rebinding to antigens upon recycling back into the plasma via FcRn, thus a single antibody molecule can repeatedly bind to multiple antigen molecules. Generally, the plasma retention of antigens is much shorter than that of antibodies with the aforementioned FcRn-regulated recycling mechanism; therefore, when antigens bind to antibodies, they typically exhibit prolonged plasma retention, leading to an increase in plasma antigen concentration. On the other hand, it has been reported that the aforementioned antibodies, which bind to antigens in a pH-dependent manner, can eliminate antigens from the plasma more rapidly than typical antibodies because they dissociate from antigens intracellularly during the FcRn-regulated recycling step. Patent Document 13 also describes computer simulation analysis showing that antibodies with pH-dependent binding against anti-C5 can prolong antigen knockdown. [List of Citations] [Patent Documents] [Patent Document 1] US Patent No. 6,355,245 [Patent Document 2] US Patent No. 7,432,356 [Patent Document 3] WO 2005 / 074607 [Patent Document 4] WO 2007 / 106585 [Patent Document 5] WO 2008 / 069889 [Patent Document 6] WO 2010 / 054403 [Patent Document 7] WO 95 / 29697 [Patent Document 8] WO 02 / 30985 [Patent Document 9] WO 2004 / 007553 [Patent Document 10] WO 2010 / 015608 [Patent Document 11] WO 2009 / 125825 [Patent Document 12] WO 2011 / 122011 [Patent Document 13] WO 2011 / 111007 [Non-patent literature] [Non-Patent Literature 1] Holers et al., Immunol. Rev. 223:300-316 (2008) [Non-Patent Literature 2] Dmytrijuk et al., The Oncologist 13(9):993-1000 (2008) [Non-Patent Literature 3] Yeung et al., J Immunol. 182(12): 7663-7671 (2009) [Non-Patent Literature 4] Datta-Mannan et al., J Biol. Chem. 282(3): 1709-1717 (2007) [Non-Patent Literature 5] Dall'Acqua et al., J. Immunol.169(9):5171-5180 (2002) [Technical Issues] One objective of this invention is to provide an anti-C5 antibody and its method of use. [Solution to the Problem] This invention provides an anti-C5 antibody and its method of use. In some embodiments, the isolated anti-C5 antibody of the present invention binds to the epitope of the β chain of C5. In some embodiments, the isolated anti-C5 antibody of the present invention binds to the epitope in the MG1-MG2 domain of the β chain of C5. In some embodiments, the isolated anti-C5 antibody of the present invention binds to the epitope in the fragment composed of amino acids 33-124 of the β chain of C5 (Sequence Identification Number: 40). In some embodiments, the isolated anti-C5 antibody of the present invention binds to the epitope in the β chain of C5 (Sequence Identification Number: 40), which includes at least one fragment selected from the group consisting of amino acids 47-57, 70-76, and 107-110. In some embodiments, the isolated anti-C5 antibody of the present invention binds to an antigenic determinant in a fragment of the β chain (Sequence Identification Number: 40) of C5, comprising at least one amino acid residue selected from the group consisting of Glu48, Asp51, His70, His72, Lys109, and His110 of Sequence Identification Number: 40. In still other embodiments, the antibody binds to C5 with higher affinity at neutral pH than at acidic pH. In still other embodiments, the antibody binds to C5 with higher affinity at pH 7.4 than at pH 5.8. In yet other embodiments, the isolated anti-C5 antibody of the present invention binds to the same antigenic determinant as the antibodies described in Table 2. In still other embodiments, the antibody binds to the same antigenic determinant as the antibodies described in Table 2 with higher affinity at pH 7.4 than at pH 5.8. In yet other embodiments, the isolated anti-C5 antibody of the present invention binds to the same antigenic determinant as the antibodies described in Table 7 or 8. In some other embodiments, the antibody binds with higher affinity to the same antigenic determinant as the antibody described in Table 7 or 8 at pH 7.4 compared to pH 5.8. In specific embodiments, the anti-C5 antibody of the present invention comprises VH and VL selected from (a) sequence identification number: 1 and sequence identification number: 11; (b) sequence identification number: 5 and sequence identification number: 15; (c) sequence identification number: 4 and sequence identification number: 14; (d) sequence identification number: 6 and sequence identification number: 16; (e) sequence identification number: 2 and sequence identification number: 12; (f) sequence identification number: 3 and sequence identification number: 13; (g) sequence identification number: 9 and sequence identification number: 19; (h) sequence identification number: 7 and sequence identification number: 17; (i) Antibodies competing for binding to C5 are used in the VH and VL pairs of sequence identifier: 8 and 18; and (j) the VH and VL pairs of sequence identifier: 10 and 20. In some embodiments, the anti-C5 antibody binds to C5 with higher affinity at neutral pH than at acidic pH. In some other embodiments, the anti-C5 antibody binds to C5 with higher affinity at pH 7.4 than at pH 5.8. In some embodiments, the isolated anti-C5 antibody of the present invention has characteristics selected from the group consisting of: (a) the antibody contacts amino acids D51 and K109 of C5 (Sequence Identification Number: 39); (b) the antibody has a greater affinity for C5 (Sequence Identification Number: 39) than for a C5 mutant consisting of an E48A substitution in Sequence Identification Number: 39; or (c) the antibody binds to the C5 protein consisting of the amino acid sequence of Sequence Identification Number: 39 at pH 7.4, but does not bind to the C5 protein consisting of the amino acid sequence of Sequence Identification Number: 39 having an H72Y substitution at pH 7.4. In still other embodiments, the antibody binds to C5 with higher affinity at neutral pH than at acidic pH. In still other embodiments, the antibody binds to C5 with higher affinity at pH 7.4 than at pH 5.8. In some embodiments, the anti-C5 antibody isolated by the present invention inhibits the activation of C5. In some embodiments, the anti-C5 antibody isolated by the present invention inhibits the activation of the C5 variant R885H. In some embodiments, the anti-C5 antibody isolated by the present invention is a monoclonal antibody. In some embodiments, the anti-C5 antibody isolated by the present invention is a human, humanized, or chimeric antibody. In some embodiments, the anti-C5 antibody isolated by the present invention is an antibody fragment bound to C5. In some embodiments, the anti-C5 antibody isolated by the present invention is a full-length IgG1 or IgG4 antibody. In some embodiments, the isolated anti-C5 antibody of the present invention comprises (a) HVR-H3, including the amino acid sequence DX. 1GYX 2X 3PTHAMX 4X 5, where X 1 represents G or A, X 2 represents V, Q, or D, X 3 represents T or Y, X 4 represents Y or H, X 5 is L or Y (sequence identification number: 128); (b) HVR-L3, including the amino acid sequence QX 1TX 2VGSSYGNX 3, where X 1 represents S, C, N, or T, X 2 is F or K, X 3 is A, T, or H (sequence identification number: 131); and (c) HVR-H2, including amino acid sequence X. 1IX 2TGSGAX 3YX 4AX 5WX 6KG, of which X 1 is C, A, or G, X 2 represents Y or F, X 3 represents T, D, or E, X 4 represents Y, K, or Q, X 5 represents S, D, or E, X 6 represents A or V (sequence identification number: 127). In some embodiments, the isolated anti-C5 antibody of the present invention comprises (a) HVR-H1, including the amino acid sequence SSYYX. 1X 2, where X 1 represents M or V, X 2 is C or A (sequence identification number: 126); (b) HVR-H2, including amino acid sequence X 1IX 2TGSGAX 3YX 4AX 5WX 6KG, of which X 1 is C, A, or G, X 2 represents Y or F, X 3 represents T, D, or E, X 4 represents Y, K, or Q, X 5 represents S, D, or E, X 6 is A or V (sequence identification number: 127); and (c) HVR-H3, including the amino acid sequence DX. 1GYX 2X 3PTHAMX 4X 5, where X 1 represents G or A, X 2 represents V, Q, or D, X 3 represents T or Y, X 4 represents Y or H, X 5 represents L or Y (sequence identification number: 128). In some other embodiments, the antibody comprises (a) HVR-L1, comprising the amino acid sequence X. 1ASQX 2IX 3SX 4LA, where X 1 represents Q or R, X 2 represents N, Q, or G, X 3 represents G or S, X 4 is D, K, or S (sequence identification number: 129); (b) HVR-L2, including the amino acid sequence GASX. 1X 2X 3S, where X 1 is K, E, or T, X 2 is L or T, X 3 is A, H, E, or Q (sequence identification number: 130); and (c) HVR-L3, including the amino acid sequence QX. 1TX 2VGSSYGNX 3, where X 1 represents S, C, N, or T, X 2 is F or K, X 3 represents A, T, or H (sequence identification number: 131). In some embodiments, the isolated anti-C5 antibody of the present invention comprises (a) HVR-L1, including amino acid sequence X. 1ASQX 2IX 3SX 4LA, where X 1 represents Q or R, X 2 represents N, Q, or G, X 3 represents G or S, X 4 is D, K, or S (sequence identification number: 129); (b) HVR-L2, including the amino acid sequence GASX. 1X 2X 3S, where X 1 is K, E, or T, X 2 is L or T, X 3 is A, H, E, or Q (sequence identification number: 130); and (c) HVR-L3, including the amino acid sequence QX. 1TX 2VGSSYGNX 3, where X 1 represents S, C, N, or T, X 2 is F or K, X 3 represents A, T, or H (sequence identification number: 131). In some embodiments, the isolated anti-C5 antibody of the present invention comprises a heavy chain variable domain frame FR1, comprising an amino acid sequence with sequence identification numbers 132 to 134; FR2 comprising an amino acid sequence with sequence identification numbers 135 to 136; FR3 comprising an amino acid sequence with sequence identification numbers 137 to 139; and FR4 comprising an amino acid sequence with sequence identification numbers 140 to 141. In some embodiments, the isolated anti-C5 antibody of the present invention comprises a light chain variable domain frame FR1, comprising an amino acid sequence with sequence identification numbers 142 to 143; FR2 comprising an amino acid sequence with sequence identification numbers 144 to 145; FR3 comprising an amino acid sequence with sequence identification numbers 146 to 147; and FR4 comprising an amino acid sequence with sequence identification number 148. In some embodiments, the isolated anti-C5 antibody of the present invention comprises (a) a VH sequence having at least 95% sequence identity with an amino acid sequence of any one of sequence identification numbers 10, 106 to 110; (b) a VL sequence having at least 95% sequence identity with an amino acid sequence of any one of sequence identification numbers 20, 111 to 113; or (c) the VH sequence as described in (a) and the VL sequence as described in (b). In still other embodiments, the antibody comprises a VH sequence of any one of sequence identification numbers 10, 106 to 110. In still other embodiments, the antibody comprises a VL sequence of any one of sequence identification numbers 20, 111 to 113. The present invention provides an antibody comprising a VH sequence of any one of sequence identification numbers 10, 106 to 110 and a VL sequence of any one of sequence identification numbers 20, 111 to 113. This invention also provides isolated nucleic acids encoding the anti-C5 antibody of this invention. This invention also provides host cells comprising the nucleic acids of this invention. This invention also provides a method for manufacturing an antibody, comprising culturing the host cells of this invention to produce the antibody. The present invention further provides a method for manufacturing a primary anti-C5 antibody. In some embodiments, the method includes immunizing an animal with a polypeptide comprising the MG1-MG2 domain (sequence identification number: 43) of the β chain of C5. In some embodiments, the method includes immunizing an animal with a polypeptide comprising a region of amino acids corresponding to positions 33 to 124 of the β chain of C5 (sequence identification number: 40). In some embodiments, the method includes immunizing an animal with a polypeptide comprising at least one fragment selected from amino acids 47 to 57, 70 to 76, and 107 to 110 of the β chain of C5 (sequence identification number: 40). In some embodiments, the method includes immunizing an animal with a polypeptide comprising a fragment of the β chain of C5 (sequence identification number: 40) comprising at least one amino acid selected from Glu48, Asp51, His70, His72, Lys109, and His110. The present invention also provides a pharmaceutical formulation comprising the anti-C5 antibody of the present invention and a pharmaceutically acceptable carrier. The anti-C5 antibody of this invention can be used as a medicine. The anti-C5 antibody of this invention can be used to treat complement regulation diseases or conditions involving excessive or uncontrolled C5 activation. The anti-C5 antibody of this invention can be used to enhance the elimination of C5 from plasma. The anti-C5 antibody of this invention can be used in the manufacture of pharmaceuticals. In some embodiments, the pharmaceuticals are used to treat complement regulation diseases or conditions involving excessive or uncontrolled C5 activation. In some embodiments, the pharmaceuticals are used to enhance the elimination of C5 from the plasma. The present invention also provides a method for treating an individual having a complement regulation disease or condition involving excessive or uncontrolled C5 activation. In some embodiments, the method includes administering an effective amount of the anti-C5 antibody of the present invention to the individual. The invention also provides a method for enhancing the elimination of C5 from plasma in an individual. In some embodiments, the method includes administering an effective amount of the anti-C5 antibody of the present invention to the individual to enhance the elimination of C5 from plasma. The techniques or procedures described or cited herein are conventional methods well-known and commonly used by those skilled in the art. For example, Sambrook et al., *Molecular Cloning: A Laboratory Manual 3d edition* (2001), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; *Current Protocols in Molecular Biology* (edited by FM Ausubel et al., 2003); *The Series Methods in Enzymology* (Academic Press, Inc.): PCR 2: A Practical Approach* (edited by MJ MacPherson, BD Hames, and GR Taylor, 1995); *Antibodies, A Laboratory Manual, and Animal Cell Culture* (edited by RI Freshney, 1987); *Oligonucleotide Synthesis* (edited by MJ Gait, 1984); *Methods in Molecular Biology*, Humana Press; *Cell Biology: A Laboratory Notebook* (edited by JE Cellis, 1998), Academic Press; *Animal Cell Culture*. (RI Freshney) edited, 1987); Introduction to Cell and Tissue Culture (JP Mather and PE Roberts, 1998) Plenum Press; Cell and Tissue Culture: Laboratory Procedures (A. Doyle, JB Griffiths, and DG Newell edited, 1993-8) J. Wiley and Sons; Handbook of Experimental Immunology (DM Weir and CC Blackwell edited); Gene Transfer Vectors for Mammalian Cells (JM Miller and MPCalos (ed., 1987); PCR: The Polymerase Chain Reaction (ed., Mullis et al., 1994); Current Protocols in Immunology (ed., JE Coligan et al., 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 (ed., D. Catty, IRL Press, 1988-1989); Monoclonal Antibodies: A Practical Approach (ed., P. Shepherd and C. Dean, Oxford University Press, 2000); Using Antibodies: A Laboratory Manual (E. Harlow and D. Lane (Cold Spring Harbor Laboratory Press, 1999); The Antibodies (M. Zanetti and JD. The widely used methods described in Capra (edited, Harwood Academic Publishers, 1995) and Cancer: Principles and Practice of Oncology (edited by VT DeVita et al., JB Lippincott Company, 1993) are as follows. I. Definitions. Unless otherwise defined, the technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Singleton et al., *Dictionary of Microbiology and Molecular Biology*, 2nd ed., J. Wiley & Sons (New York, NY 1994), and *March, Advanced Organic Chemistry Reactions, Mechanisms and Structure*, 4th ed., John Wiley & Sons (New York, NY 1992) provide general guidance to those skilled in the art regarding many of the terms used in this application. All references cited herein, including patent applications and publications, are incorporated herein by reference in their entirety. For the purpose of interpreting this specification, the following definitions will be used, and terms used in the singular may also include plural forms, and vice versa, where appropriate. It should be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. In the event of any conflict between any of the definitions set forth below and any reference incorporated herein by reference, the definitions below shall prevail. For the purposes of this document, a “receptor human frame” is a frame comprising an amino acid sequence of a light chain variable domain (VL) frame or a heavy chain variable domain (VH) frame derived from the human immunoglobulin frame or the human common frame as defined below. A receptor human frame “derived from” the human immunoglobulin frame or the human common frame may include its same amino acid sequence, or it may include amino acid sequence alterations. In some embodiments, the number of amino acid alterations is 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, or 2 or fewer. In some embodiments, the VL receptor human frame is sequence-identical to the VL human immunoglobulin frame sequence or the human common frame sequence. “Affinity” refers to the total strength of the non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless otherwise stated, “binding affinity” as used herein refers to intrinsic binding affinity, which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of molecule X for its partner Y can generally be expressed by the dissociation constant (Kd). Affinity can be measured by methods known in the art, including those described herein. Specific descriptions and exemplary embodiments for measuring binding affinity are described below. "Affinity-matured" antibodies are those that have one or more alterations in one or more hypervariable regions (HVRs) compared to parent antibodies that do not have such alterations. These alterations result in improved antibody affinity for the antigen. The terms "anti-C5 antibody" and "antibody bound to C5" refer to an antibody that binds to C5 with sufficient affinity so that the antibody can be used as a diagnostic and / or therapeutic agent targeting C5. In one embodiment, for example by radioimmunoassay (RIA), the degree to which the anti-C5 antibody binds to unrelated non-C5 proteins is less than about 10% of the antibody's binding to C5. In specific embodiments, the antibody bound to C5 has ≤1 μM, ≤100 nM, ≤10 nM, ≤1 nM, ≤0.1 nM, ≤0.01 nM, or ≤0.001 nM (e.g., 10 μM). -8 M or smaller, for example, by 10 -8 M to 10 -13 M, for example, from 10 -9 M to 10 -13 The dissociation constant (Kd) of M). In a specific embodiment, the anti-C5 antibody binds to the antigenic determinant of C5, which is conserved with C5 from different species. The term “antibody” is used in the broadest sense herein and covers a variety of antibody structures, including but not limited to monoclonal antibodies, multiclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, as long as they exhibit the desired antigen-binding activity. An "antibody fragment" refers to a molecule that includes a portion of a complete antibody, other than the complete antibody itself, and that binds to the antigen bound by that complete antibody. Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, and F(ab'). 2; diabody; linear antibody; single-chain antibody molecule (e.g., scFv); and multispecific antibody formed from antibody fragments. "Antibodies that bind to the same antigenic determinant" as a reference antibody refers to an antibody that blocks the binding of the reference antibody to its antigen in a competition assay, and / or conversely, the reference antibody blocks the binding of the antibody to its antigen in a competition assay. This document provides exemplary competition assays. The term "chimeric" antibody refers to an antibody in which part of the heavy chain and / or light chain comes from a specific source or species, while the rest of the heavy chain and / or light chain comes from different sources or species. An antibody's "type" refers to the type of constant domain or constant region possessed by its heavy chain. There are five main types of antibodies: IgA, IgD, IgE, IgG, and IgM. Several of these types can be further subdivided into subgroups (isotypes), for example, IgG... 1. IgG 2. IgG 3. IgG 4. IgA 1 and IgA 2. The heavy chain constant domains corresponding to different types of immunoglobulins are respectively called α, δ, ε, γ, and μ. As used herein, the term "cytotoxic agent" refers to a substance that inhibits or prevents cellular function and / or causes cell death or destruction. Cytotoxic agents include, but are not limited to, radioactive isotopes (e.g., At). 211 I 131 I 125 Y 90 Re 186 Re 188 、Sm 153 Bi 212 P 32 Pb 212And radioactive isotopes of Lu); chemotherapeutic agents or drugs (e.g., methotrexate, adriamicin, vincristine, vinblastine, etoposide, doxorubicin, melphalan, mitomycin C, chlorambucil, daunorubicin or other intercalating agents); growth inhibitors; enzymes and their fragments, such as nucleolysins; antibiotics; toxins, such as small molecule toxins or enzyme-active toxins of bacterial, fungal, plant or animal origin, including their fragments and / or variants; and a variety of antitumor or anticancer agents disclosed below. "Effective function" refers to those biological activities attributable to the Fc region of an antibody, which vary with antibody isotype. Examples of antibody effector functions include: Clq binding and complement-dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; negative regulation of cell surface receptors (e.g., B cell receptors); and B cell activation. The "effective amount" of a reagent, such as a pharmaceutical formulation, refers to the amount that, at the required dosage and within the required time, is effective in achieving the desired therapeutic or preventative outcome. The term "antigen determinant" encompasses any determinant that can be bound by an antibody. An antigen determinant is a region of the antigen that is bound by an antibody targeting that antigen, and contains a specific amino acid that directly contacts the antibody. Antigen determinant sites may comprise chemically active surface clusters of molecules (e.g., amino acids, sugar branches, phosphate groups, or sulfonyl groups) and may possess specific three-dimensional structural characteristics and / or specific charge characteristics. Generally, antibodies specific to a particular target antigen will preferentially recognize antigen determinants on the target antigen in complex mixtures of proteins and / or macromolecules. The term "Fc region" used herein is used to define the C-terminal region of the immunoglobulin heavy chain, which comprises at least a portion of the constant region. This term includes both native sequence Fc regions and variant Fc regions. In one embodiment, the human IgG heavy chain Fc region extends from Cys226 or Pro230 to the C-terminus of the heavy chain. However, the C-terminal lysine (Lys447) or glycine-lysine (residues 446-447) of the Fc region may or may not be present. Unless otherwise stated herein, the amino acid residues in the Fc region or constant region are numbered according to the EU numbering system, also known as the EU index, as described by Kabat et al. Described in Sequences of Proteins of Immunological Interest 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991. "Frame" or "FR" refers to the variable domain residues outside the highly variable region (HVR) residues. The variable domain FR is generally composed of four FR domains: FR1, FR2, FR3, and FR4. Therefore, the HVR and FR sequences generally appear in VH (or VL) in the following order: FR1-H1(L1)-FR2-H2(L2)-FR3-H3(L3)-FR4. The terms “full-length antibody,” “intact antibody,” and “all antibody” are used interchangeably in this document to refer to an antibody that has a structure substantially similar to that of a natural antibody or that has a heavy chain containing the Fc region as defined herein. The terms "host cell," "host cell line," and "host cell culture" are used interchangeably to refer to cells in which exogenous nucleic acids have been introduced, including progeny cells. Host cells include "transformers" and "transformed cells," which include the initially transformed cells and their derived progeny, regardless of passage number. The nucleic acid content of progeny cells may not be identical to that of the parent cells and may contain mutations. This article includes mutant progeny cells with the same function or biological activity as those screened or selected in the initially transformed cells. "Human antibody" is an antibody having an amino acid sequence corresponding to an antibody produced by humans or human cells or derived from a non-human source, wherein the non-human source amino acid sequence is encoded by a human antibody library or other human antibody sequences. This definition of human antibody specifically excludes humanized antibodies that include non-human antigen-binding residues. The "human common framework" is a framework representing the most frequently occurring amino acid residues in the selection of the VL or VH framework sequence of human immunoglobulins. Generally, the selection of the VL or VH sequence of human immunoglobulins is derived from a isotype of the variable domain sequence. Typically, the isotype is that of Kabat et al. Sequences of Proteins of Immunological Interest, Fifth Edition, NIH Publication 91-3242, Bethesda MD (1991), vols. 1-3. In one embodiment, for VL, the subtype is as described by Kabat et al. The subtype kappa I in supra. In one embodiment, for VH, the subtype is as described by Kabat et al. Subtype III in supra. "Humanized" antibodies refer to chimeric antibodies comprising amino acid residues from non-human HVRs and amino acid residues from human FRs. In certain embodiments, a humanized antibody will include at least one, and typically two, variable domains, wherein all or substantially all of the HVRs (e.g., CDRs) correspond to those of non-human antibodies, and all or substantially all of the FRs correspond to those of human antibodies. Humanized antibodies may optionally include at least a portion of the antibody constant region derived from a human antibody. The "humanized form" of an antibody (e.g., a non-human antibody) refers to an antibody that has been humanized. As used herein, the term “hypervariant region” or “HVR” refers to each region of an antibody variable domain that is highly variable in sequence (“complementarity-determining region” or “CDR”), and / or forms a structurally defined loop (“hypervariant loop”), and / or contains antigen contact residues (“antigen contact”). Generally, an antibody comprises six HVRs: three in VH (H1, H2, H3) and three in VL (L1, L2, L3). Exemplary HVRs in this document include: (a) those 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, (a) Highly variable rings appearing at 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., J. Mol. Biol. 196:901-917 (1987)); (b) Appearing at 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., (c) CDRs of Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, NIH, Bethesda, MD (1991); appearing at 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., The antigen contact of J. Mol. Biol.262:732-745 (1996)); and (d) combinations of (a), (b) and / or (c), comprising HVR amino acid residues 46-56(L2), 47-56(L2), 48-56(L2), 49-56(L2), 26-35(H1), 26-35b(H1), 49-65(H2), 93-102(H3) and 94-102(H3). Unless otherwise stated, HVR residues and other residues in the variable domain (e.g., FR residues) in this paper are in accordance with Kabat et al. supra number. "Immunoconjugates" are antibodies conjugated to one or more heterogeneous molecules (including, but not limited to, cytotoxic agents). "Individual" or "subject" is a mammal. Mammals include, but are not limited to, domesticated animals (e.g., cattle, sheep, cats, dogs, and horses), primates (e.g., humans and non-human primates such as monkeys), rabbits, and rodents (e.g., mice and rats). In a particular embodiment, the individual or object is a human. "Isolated" antibodies are antibodies that have been separated from components of their natural environment. In some embodiments, antibodies are purified to a purity greater than 95% or 99%, determined by methods such as electrophoresis (e.g., SDS-PAGE, isoelectric focusing (IEF), capillary electrophoresis) or chromatography (e.g., ion exchange or reversed-phase HPLC). A review of methods for assessing antibody purity can be found, for example, in Flatman et al. J. Chromatogr. B848:79-87 (2007). "Isolated" nucleic acids refer to nucleic acid molecules that have been separated from components of their natural environment. Isolated nucleic acids include nucleic acid molecules that are normally contained in cells, but which are located outside the chromosome or at a chromosomal location different from their natural chromosomal location. "Isolated nucleic acid encoding anti-C5 antibody" refers to one or more nucleic acid molecules encoding the heavy and light chains (or fragments thereof) of the antibody, contained in a single or separate vector, or present at one or more locations in the host cell. As used herein, the term "monoclonal antibody" refers to an antibody obtained from a substantially homogeneous antibody family, i.e., a single antibody comprising the same family and / or binding to the same antigenic determinant, except, for example, antibodies containing naturally occurring mutations or possible variants that may arise during the preparation of monoclonal antibodies (such variants are typically present in small amounts). Unlike the preparation of polyclonal antibodies, which typically comprises different antibodies targeting different determinants (antigenic determinants), each monoclonal antibody prepared targets a single determinant on the antigen. Therefore, the modifier "monoclonal" refers to the antibody characteristics obtained from a substantially homogeneous antibody family and is not construed as requiring any specific method to produce the antibody. For example, monoclonal antibodies to be used according to the present invention can be prepared by a variety of techniques, including but not limited to fusion tumor technology, recombinant DNA methods, phage display methods, and methods using transgenic animals containing all or part of the human immunoglobulin locus (LOCI), such methods and other exemplary methods for producing monoclonal antibodies will be described herein. "Naked antibody" refers to an antibody that is not conjugated to a heterologous portion (such as a cytotoxic portion) or a radiolabel. Naked antibodies can be present in pharmaceutical formulations. "Natural antibodies" refer to naturally occurring immunoglobulin molecules with different structures. For example, natural IgG antibodies are heterotetrameric glycoproteins of approximately 150,000 daltons, composed of two identical light chains and two identical heavy chains linked by disulfide bonds. From the N to the C-terminus, each heavy chain has a variable region (VH), also called a variable heavy chain domain or heavy chain variable domain, followed by three constant domains (CH1, CH2, and CH3). Similarly, from the N to the C-terminus, each light chain has a variable region (VL), also called a variable light chain domain or light chain variable domain, followed by a constant light chain (CL) domain. Based on the amino acid sequence of their constant domains, the light chains of antibodies can be classified into one of two types, called κ and λ. The term "package insert" refers to the instructions typically included in the commercial packaging of a therapeutic product, which contain information about indications, usage, dosage, administration, combination therapy, contraindications, and / or warnings regarding the use of such therapeutic products. The "percentage (%) amino acid sequence identity" relative to a reference polypeptide sequence is defined as the percentage of amino acid residues in the candidate sequence that are identical to those in the reference polypeptide sequence, after sequence alignment and, where necessary, the introduction of gaps to achieve maximum percentage sequence identity, without considering any conservative substitutions as part of the sequence identity. Alignment for the purpose of determining percentage amino acid sequence identity can be achieved in various ways within the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, Megalign (DNASTAR) software, or GENTYX (registered trademark) (Genetyx Co., Ltd.). Those skilled in the art can determine the appropriate parameters for sequence alignment, including any algorithm required to achieve maximum alignment across the full length of the sequences being compared. The ALIGN-2 sequence comparison computer program was written by Genentech, Inc., and the source code has been submitted with the user file to the U.S. Copyright Office, Washington DC, 20559, and is registered with the U.S. Copyright Office under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available at Genentech, Inc., South San Francisco, California, or can be compiled from the source code. The ALIGN-2 program should be compiled for use on UNIX operating systems, including digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and remain unchanged. When using ALIGN-2 for amino acid sequence comparison, the % amino acid sequence identity of a given amino acid sequence A compared to and / or relative to a given amino acid sequence B (or it can be expressed as a given amino acid sequence A having or including a specific % amino acid sequence identity compared to and / or relative to a given amino acid sequence B) is calculated as follows: 100 multiplied by the fraction X / Y, where X is the number of amino acid residues scored as a match by the sequence alignment program ALIGN-2 in the A and B alignments, and Y is the total number of amino acid residues in B. It should be understood that when the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A compared to B will not be equal to the % amino acid sequence identity of B compared to A. Unless explicitly stated otherwise, all % amino acid sequence identity values ​​used herein are obtained using the ALIGN-2 computer program as described in the preceding paragraphs. The term "pharmaceutical formulation" refers to a preparation in a form in which the bioactivity of the active ingredient contained therein is permitted and which does not contain any additional ingredients that would have unacceptable toxicity to the subject to which the formulation will be applied. "Pharmaceutical acceptable carriers" refer to a component in a pharmaceutical formulation other than the active ingredient that is non-toxic to the target organism. Pharmaceutical acceptable carriers include, but are not limited to, buffers, excipients, stabilizers, or preservatives. As used herein, the term "C5" encompasses any naturally occurring C5 from any vertebrate source, including mammals such as primates (e.g., humans and monkeys) and rodents (e.g., mice and rats). Unless otherwise stated, the term "C5" refers to the human C5 protein having the amino acid sequence shown in Sequence Identifier: 39 and containing the β-chain sequence shown in Sequence Identifier: 40. This term encompasses "full-length" untreated C5 and any form of C5 produced by intracellular processing. This term also encompasses naturally occurring variants of C5, such as splice variants or allelic variants. An exemplary human C5 amino acid sequence is shown in Sequence Identifier: 39 ("wild-type" or "WT" C5). An exemplary human C5 β-chain amino acid sequence is shown in Sequence Identifier: 40. The amino acid sequences of the MG-1, MG-2, and MG1-MG2 domains of the β chain of the exemplary human C5 are shown in sequence identification numbers 41, 42, and 43, respectively. The amino acid sequences of the exemplary rhesus monkey and mouse C5 are shown in sequence identification numbers 44 and 105, respectively. Amino acid residues 1 to 19 of sequence identification numbers 39, 40, 43, 44, and 105 correspond to message sequences that are removed during intracellular processing and therefore do not appear in the corresponding exemplary amino acid sequences. As used herein, “treatment” (and its grammatical variations) refers to a clinical intervention that attempts to alter the natural course of disease in the treated individual, and can be carried out for prevention or during clinicopathological processes. Desired treatment effects include, but are not limited to, preventing the onset or recurrence of disease, alleviating symptoms, reducing any direct or indirect pathological outcome of the disease, preventing metastasis, slowing the rate of disease progression, improving or mitigating the disease state, and reducing or improving prognosis. In some embodiments, the antibodies of the present invention are used to delay the development of disease or slow its progression. The term "variable region" or "variable domain" refers to a domain of the antibody heavy or light chain involved in the binding of the antibody to the antigen. The variable domains (VH and VL, respectively) of the heavy and light chains of natural antibodies typically have similar structures, with each domain comprising four conserved frame regions (FRs) and three highly variable regions (HVRs) (see, for example, Kindt et al.). Kuby Immunology, 6 th(ed., WH Freeman and Co., p. 91 (2007)). A single VH or VL domain may be sufficient to confer specificity for antigen binding. Furthermore, antibodies binding to a specific antigen can be isolated by screening complementary VL or VH domain databases using the VH or VL domain of the antibody binding to that antigen. See, for example, Portolano et al. J. Immunol. 150:880-887 (1993); Clarkson et al. Nature 352:624-628 (1991). As used herein, the term "vector" refers to a nucleic acid molecule capable of replicating another nucleic acid linked to it. This term encompasses vectors that function as autonomously replicating nucleic acid structures, as well as vectors incorporated into the genome of a host cell to which they have been introduced. Specific vectors can indicate the expression of the nucleic acids to which they are effectively linked. These types of vectors are referred to herein as "expression vectors." II. Composition and Methods In one embodiment, the invention is, in part, based on anti-C5 antibodies and their use. In a particular embodiment, an antibody binding to C5 is provided. The antibodies of the present invention are beneficial, for example, in the diagnosis and treatment of complement regulation diseases or conditions involving excessive or uncontrolled C5 activation. A. Exemplary anti-C5 antibody In one embodiment, the invention provides an antibody that binds to the isolated C5. In a particular embodiment, the anti-C5 antibody of the present invention binds to an antigenic determinant within the β chain of C5. In a particular embodiment, the anti-C5 antibody binds to an antigenic determinant within the MG1-MG2 domain of the β chain of C5. In a particular embodiment, the anti-C5 antibody binds to an antigenic determinant within a fragment composed of amino acids 19 to 180 of the β chain of C5. In a particular embodiment, the anti-C5 antibody binds to an antigenic determinant within the MG1 domain (sequence identification number: 40 (sequence identification number: 41) of the β chain of C5, specifically amino acids 20 to 124. In a particular embodiment, the anti-C5 antibody binds to an antigenic determinant within a fragment composed of amino acids 33 to 124 of the β chain of C5 (sequence identification number: 40). In another embodiment, the anti-C5 antibody does not bind to a fragment shorter than the segment composed of amino acids 33 to 124 of the β chain of C5, for example, a segment composed of amino acids 45 to 124, 52 to 124, 33 to 111, 33 to 108, or 45 to 111 of the β chain of C5 (Sequence Identification Number: 40). In another embodiment, the invention provides an anti-C5 antibody exhibiting pH-dependent binding properties. As used herein, the term "pH-dependent" means that the antibody exhibits "reduced binding to C5 at acidic pH compared to neutral pH" (the two terms may be used interchangeably for the purposes of this disclosure). For example, an antibody "having pH-dependent binding properties" comprises an antibody that binds to C5 with higher affinity at neutral pH compared to acidic pH. In certain embodiments, the antibodies of the present invention bind to C5 at neutral pH with an affinity of 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 compared to acidic pH. In some embodiments, the antibody binds to C5 at pH 7.4 with higher affinity compared to pH 5.8. In some other embodiments, compared to pH 5.8, the antibody of the present invention binds to C5 with an affinity of 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 at pH 7.4. For the purposes of this disclosure, the “affinity” of an antibody to C5 is expressed in the terminology of the antibody’s KD. The KD of an antibody refers to the equilibrium dissociation constant of the antibody-antigen interaction. The higher the KD value of an antigen binding to its antigen, the weaker its affinity for that particular antigen. Therefore, as used herein, “higher affinity at neutral pH than at acidic pH” (or equivalently, “pH-dependent binding”) means that the KD of the antibody binding to C5 at acidic pH is greater than the KD of the antibody binding to C5 at neutral pH. For example, in the context of this invention, if the KD of the antibody binding to C5 at acidic pH is at least twice greater than the KD of the antibody binding to C5 at neutral pH, the antibody is considered to bind to C5 with higher affinity at neutral pH than at acidic pH. Therefore, the present invention includes antibodies whose KD at acidic pH binding to C5 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 at neutral pH binding to C5. 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 an acidic pH may be 10. -9 M, 10 -8 M, 10 -7 M, 10 -6 M or larger. In some other embodiments, if the KD of the antibody binding to C5 at pH 5.8 is at least twice greater than the KD of the antibody binding to C5 at pH 7.4, the antibody is considered to bind to C5 with higher affinity at neutral pH compared to acidic pH. In some embodiments, the provided antibody has a KD of 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 than the KD of the antibody binding to C5 at pH 7.4. In another embodiment, the KD value of the antibody at pH 7.4 may be 10. -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M, 10 -12 M or smaller. In another embodiment, the KD value of the antibody at pH 5.8 may be 10. -9 M, 10 -8 M, 10 -7 M, 10 -6 M or larger. The binding properties of an antibody to a specific antigen can also be represented by the antibody's kd. The antibody's kd refers to the dissociation rate constant of the antibody against a specific antigen, expressed as the reciprocal of seconds (i.e., sec). -1An increased kd value indicates weaker binding of the antibody to its antigen. Therefore, this invention includes antibodies that bind to C5 at acidic pH with a higher kd value compared to neutral pH. This invention includes antibodies whose kd value for binding to C5 at acidic pH 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 their kd value for binding to C5 at neutral pH. In another embodiment, the kd value of the antibody at neutral pH 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 embodiment, the antibody's kd value can be 10 at an acidic pH. -3 1 / s, 10 -2 1 / s, 10 -1 1 / s or greater. The present invention also includes antibodies that bind to C5 at pH 5.8 with a larger kd value compared to those at pH 7.4. The present invention includes antibodies whose kd value for binding to C5 at pH 5.8 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 that for binding to C5 at pH 7.4. In another embodiment, the kd value of the antibody 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 embodiment, the antibody may have a kd value of 10 at pH 5.8. -3 1 / s, 10 -2 1 / s, 10 -1 1 / s or greater. In certain embodiments, "reduced binding to C5 at acidic pH compared to neutral pH" is expressed as 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, for the purposes of this invention, if an antibody has an acidic / neutral KD ratio of 2 or greater, then the antibody can be considered to have "reduced binding to C5 at acidic pH compared to neutral pH." In some specific exemplary embodiments, the pH 5.8 / pH 7.4 KD ratio of the antibody of this invention may be 2 or greater. In some specific exemplary embodiments, the acid / neutral KD ratio of the 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 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 an acidic pH may be 10. -9 M, 10 -8 M, 10 -7 M, 10 -6 M or greater. In a further example, for the purposes of this invention, if the pH 5.8 / pH 7.4 KD ratio of the antibody is 2 or greater, the antibody can be considered to have "reduced binding to C5 at acidic pH compared to neutral pH". In some specific exemplary embodiments, the pH 5.8 / pH 7.4 KD ratio of the antibody of this invention can 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 greater. In another embodiment, 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 smaller. In another embodiment, the KD value of the antibody at pH 5.8 may be 10. -9 M, 10 -8 M, 10 -7 M, 10 -6 M or larger. In certain examples, "reduced binding to C5 at acidic pH compared to neutral pH" is expressed as 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, for the purposes of this invention, if an antibody has an acidic / neutral kd ratio of 2 or greater, then the antibody can be considered to have "reduced binding to C5 at acidic pH compared to neutral pH." In some specific exemplary embodiments, the pH 5.8 / pH 7.4 kd ratio of the antibody of this invention may be 2 or greater. In some specific exemplary embodiments, the acidic / neutral kd ratio of the antibody of this 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 some other embodiments, the pH 5.8 / pH 7.4 kd ratio of the antibody can 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 can be 10. -2 1 / s, 10 -3 1 / s, 10 -4 1 / s, 10 -5 1 / s, 10 -6 1 / s or less. In yet another embodiment, the antibody may have a kd value of 10 at pH 7.4. -2 1 / s, 10 -3 1 / s, 10 -4 1 / s, 10 -5 1 / s, 10 -6 1 / s or less. In another embodiment, the kd value of the antibody at acidic pH may be 10. -3 1 / s, 10 -2 1 / s, 10 -1 1 / s or greater. In yet another embodiment, the antibody may have a kd value of 10 at pH 5.8. -3 1 / s, 10 -2 1 / s, 10 -1 1 / s or greater. As used herein, the term "acidic pH" refers to a pH range of 4.0 to 6.5. The term "acidic pH" includes any pH value among 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 a specific sample, "acidic pH" is 5.8. As used herein, the term "neutral pH" refers to a pH between 6.7 and 10.0. The term "neutral pH" includes any pH value from 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 a specific sample, "neutral pH" is 7.4. KD and kd values, as indicated herein, can be determined using a biosensor based on surface plasma resonance to characterize antibody-antigen interactions (see, for example, Example 3 herein). KD and kd values ​​can be measured at 25°C or 37°C. In a specific embodiment, the anti-C5 antibody of the present invention binds to an antigenic determinant within the β chain of C5, which is composed of an MG1 domain (Sequence Identification Number: 41). In a specific embodiment, the anti-C5 antibody of the present invention binds to an antigenic determinant within the β chain of C5 (Sequence Identification Number: 40), which includes at least one fragment selected from the group consisting of amino acids 47-57, 70-76, and 107-110. In a specific embodiment, the anti-C5 antibody of the present invention binds to an antigenic determinant within a fragment of the β chain of C5 (Sequence Identification Number: 40), which includes at least one amino acid selected from the group consisting of Thr47, Glu48, Ala49, Phe50, Asp51, Ala52, Thr53, Lys57, His70, Val71, His72, Ser74, Glu76, Val107, Ser108, ​​Lys109, and His110. In a particular embodiment, the anti-C5 antibody of the present invention binds to an antigenic determinant within a fragment of the β chain (sequence identification number: 40) of C5, comprising at least one amino acid selected from the group consisting of Glu48, Asp51, His70, His72, Lys109, and His110. In a particular embodiment, the anti-C5 antibody of the present invention exhibits reduced binding to C5 mutants compared to its binding to wild-type C5, wherein the C5 mutant has at least one amino acid substituted at a position selected from the group consisting of Glu48, Asp51, His72, and Lys109. In another embodiment, the anti-C5 antibody of the present invention exhibits reduced pH-dependent binding to C5 mutants compared to its pH-dependent binding to wild-type C5, wherein the C5 mutant has at least one amino acid substituted at a position selected from the group consisting of His70, His72, and His110. In another embodiment, in the C5 mutant, amino acids selected from Glu48, Asp51 and Lys109 are replaced by alanine, and amino acids selected from His70, His72 and His110 are replaced by tyrosine. In a specific embodiment, the anti-C5 antibody of the present invention and an antibody competitively bind to C5, the antibody comprising: (a) VH of sequence identifier: 1 and VL of sequence identifier: 11; (b) VH of sequence identifier: 22 and VL of sequence identifier: 26; (c) VH of sequence identifier: 21 and VL of sequence identifier: 25; (d) VH of sequence identifier: 5 and VL of sequence identifier: 15; (e) VH of sequence identifier: 4 and VL of sequence identifier: 14; (f) VH of sequence identifier: 6 and VL of sequence identifier: 16; (g) VH of sequence identifier: 2 and VL of sequence identifier: 15. VL of sequence identifier: 12; (h) VH of sequence identifier: 3 and VL of sequence identifier: 13; (i) VH of sequence identifier: 9 and VL of sequence identifier: 19; (j) VH of sequence identifier: 7 and VL of sequence identifier: 17; (k) VH of sequence identifier: 8 and VL of sequence identifier: 18; (l) VH of sequence identifier: 23 and VL of sequence identifier: 27; and (m) VH and VL pairs of VH and VL of sequence identifier: 10 and VL of sequence identifier: 20. In certain embodiments, the anti-C5 antibody of the present invention binds to C5 and contacts amino acid Asp51 (D51) at sequence identification number 39. In still other embodiments, the anti-C5 antibody of the present invention binds to C5 and contacts amino acid Lys109 (K109) at sequence identification number 39. In yet another embodiment, the anti-C5 antibody of the present invention binds to C5 and contacts both amino acid Asp51 (D51) and amino acid Lys109 (K109) at sequence identification number 39. In a particular embodiment, the anti-C5 antibody of the present invention exhibits reduced binding to a C5 mutant, wherein the C5 mutant has a Glu48Ala (E48A) substitution at sequence identification number 39, compared to its binding to wild-type C5. In another embodiment, the anti-C5 antibody of the present invention exhibits reduced pH-dependent binding to a C5 mutant, wherein the C5 mutant has a Glu48Ala (E48A) substitution at sequence identification number 39, compared to its pH-dependent binding to wild-type C5. In another embodiment, the anti-C5 antibody binds to the C5 protein composed of the amino acid sequence of sequence identification number 39, but not to the C5 protein composed of the amino acid sequence of sequence identification number 39 with H72Y substitution; wherein the C5 protein and the H72Y-substituted C5 protein are prepared and screened under the same conditions. In yet another embodiment, the anti-C5 antibody binds to the C5 protein composed of the amino acid sequence of sequence identification number 39 at pH 7.4, but not to the C5 protein composed of the amino acid sequence of sequence identification number 39 with H72Y substitution at pH 7.4. Without being bound by any particular theory, it can be inferred that when one amino acid residue on C5 is replaced by another amino acid, the binding of the anti-C5 antibody to C5 decreases (or almost disappears). This suggests that the amino acid residue on C5 is important for the interaction between the anti-C5 antibody and C5, and that the antibody can recognize the antigenic determinants surrounding the amino acid on C5. This invention has discovered a group of anti-C5 antibodies that compete with or bind to the same antigenic determinant, exhibiting pH-dependent binding properties. Among amino acids, histidine, with a pKa value of approximately 6.0 to 6.5, can exhibit different proton dissociation states between neutral and acidic pH. Therefore, histidine residues on C5 can contribute to the pH-dependent interaction between anti-C5 antibodies and C5. Without being limited to any particular theory, it can be hypothesized that anti-C5 antibodies can recognize conformational structures surrounding histidine residues on C5, changes of which depend on pH. This hypothesis is consistent with the following experimental results: when the histidine residues on C5 are replaced by another amino acid, the pH dependence of anti-C5 antibodies decreases (or almost disappears) (i.e., at neutral pH, anti-C5 antibodies with pH-dependent binding properties bind to histidine mutants of C5 with a similar affinity to wild-type C5, while at acidic pH, the same antibody binds to histidine mutants of C5 with a higher affinity than to wild-type C5). In certain embodiments, the anti-C5 antibody of the present invention binds to C5 from more than one species. In still other embodiments, the anti-C5 antibody binds to C5 from humans and non-human animals. In yet other embodiments, the anti-C5 antibody binds to C5 from humans and monkeys (e.g., rhesus macaques, marmosets, chimpanzees, or baboons). In one embodiment, the present invention provides an anti-C5 antibody that inhibits C5 activation. In a particular embodiment, an anti-C5 antibody is provided that prevents C5 cleavage to form C5a and C5b, thereby preventing the generation of anaphylactic toxin activity associated with C5a and also preventing the combination of the C5b-9 membrane attack complex (MAC) associated with C5b. In a particular embodiment, an anti-C5 antibody is provided that inhibits C5 convertase from converting C5 into C5a and C5b. In a particular embodiment, an anti-C5 antibody is provided that prevents C5 convertase from accessing the cleavage site on C5. In a particular embodiment, an anti-C5 antibody is provided that inhibits hemolytic activity caused by C5 activation. In still other embodiments, the anti-C5 antibody of the present invention inhibits C5 activation via classical and / or alternative pathways. In one embodiment, the present invention provides an anti-C5 antibody that inhibits the activation of C5 variants. A C5 variant refers to a variant of the C5 gene caused by gene variation, such as mutation, polymorphism, or allelic variation. Gene variation may include deletion, substitution, or insertion of one or more nucleotides. A C5 variant may include one or more gene variations in C5. In a particular embodiment, the C5 variant has biological activity similar to wild-type C5. Such a C5 variant may include at least one variant selected from the group consisting of V145I, R449G, V802I, R885H, R928Q, D966Y, S1310N, and E1437D. Here, R885H, for example, refers to a gene variation in which arginine at position 885 is replaced by histidine. In a particular embodiment, the anti-C5 antibody of the present invention inhibits the activation of wild-type C5 and at least one C5 variant selected from the group consisting of V145I, R449G, V802I, R885H, R928Q, D966Y, S1310N and E1437D. In one embodiment, the present invention provides an anti-C5 antibody comprising at least one, two, three, four, five, or six highly variable regions (HVRs) selected from (a) an amino acid sequence comprising sequence identification number 45 to 54; (b) an amino acid sequence comprising sequence identification number 55 to 64; (c) an amino acid sequence comprising sequence identification number 65 to 74; (d) an amino acid sequence comprising sequence identification number 75 to 84; (e) an amino acid sequence comprising sequence identification number 85 to 94; and (f) an amino acid sequence comprising sequence identification number 95 to 104. In one embodiment, the present invention provides an antibody comprising at least one, at least two, or all three VH HVR sequences selected from (a) HVR-H1 comprising an amino acid sequence of any one of sequence identification numbers 45 to 54; (b) HVR-H2 comprising an amino acid sequence of any one of sequence identification numbers 55 to 64; and (c) HVR-H3 comprising an amino acid sequence of any one of sequence identification numbers 65 to 74. In one embodiment, the antibody comprises HVR-H3 comprising an amino acid sequence of any one of sequence identification numbers 65 to 74, and HVR-L3 comprising an amino acid sequence of any one of sequence identification numbers 95 to 104. In another embodiment, the antibody includes HVR-H3, which includes an amino acid sequence with sequence identification numbers 65 to 74; HVR-L3, which includes an amino acid sequence with sequence identification numbers 95 to 104; and HVR-H2, which includes an amino acid sequence with sequence identification numbers 55 to 64. In yet another embodiment, the antibody includes (a) HVR-H1, which includes an amino acid sequence with sequence identification numbers 45 to 54; (b) HVR-H2, which includes an amino acid sequence with sequence identification numbers 55 to 64; and (c) HVR-H3, which includes an amino acid sequence with sequence identification numbers 65 to 74. In another embodiment, the present invention provides an antibody comprising at least one, at least two, or all three VL HVR sequences selected from (a) an HVR-L1 comprising an amino acid sequence of sequence identification number: any one of sequence identification numbers: 75 to 84; (b) an HVR-L2 comprising an amino acid sequence of sequence identification number: any one of sequence identification numbers: 85 to 94; and (c) an HVR-L3 comprising an amino acid sequence of sequence identification number: any one of sequence identification numbers: 95 to 104. In one embodiment, the antibody comprises (a) an HVR-L1 comprising an amino acid sequence of sequence identification number: any one of sequence identification numbers: 75 to 84; (b) an HVR-L2 comprising an amino acid sequence of sequence identification number: any one of sequence identification numbers: 85 to 94; and (c) an HVR-L3 comprising an amino acid sequence of sequence identification number: any one of sequence identification numbers: 95 to 104. In another embodiment, the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three selected from (i) HVR-H1 comprising an amino acid sequence of any one of sequence identification numbers 45 to 54, (ii) HVR-H2 comprising an amino acid sequence of any one of sequence identification numbers 55 to 64, and (iii) HVR-H3 comprising an amino acid sequence of any one of sequence identification numbers 65 to 74; and (b) a VL domain comprising at least one, at least two, or all three selected from (i) HVR-L1 comprising an amino acid sequence of any one of sequence identification numbers 75 to 84, (ii) HVR-L2 comprising an amino acid sequence of any one of sequence identification numbers 85 to 94, and (c) HVR-L3 comprising an amino acid sequence of any one of sequence identification numbers 95 to 104. In another embodiment, the present invention provides an antibody comprising (a) HVR-H1 comprising an amino acid sequence of sequence identification number 45 to 54; (b) HVR-H2 comprising an amino acid sequence of sequence identification number 55 to 64; (c) HVR-H3 comprising an amino acid sequence of sequence identification number 65 to 74; (d) HVR-L1 comprising an amino acid sequence of sequence identification number 75 to 84; (e) HVR-L2 comprising an amino acid sequence of sequence identification number 85 to 94; and (f) HVR-L3 comprising an amino acid sequence of sequence identification number 95 to 104. In one embodiment, the present invention provides a primary anti-C5 antibody comprising at least one, two, three, four, five, or six amino acid sequences selected from (a) HVR-H1 comprising any of the amino acid sequences identified by sequence identification numbers 45, 54, 117, and 126; (b) HVR-H2 comprising any of the amino acid sequences identified by sequence identification numbers 55, 64, 118-120, and 127; (c) HVR-H3 comprising any of the amino acid sequences identified by sequence identification numbers 65, 74, 121, and 128; (d) HVR-L1 comprising any of the amino acid sequences identified by sequence identification numbers 75, 84, 122, and 129; (e) HVR-L2 comprising any of the amino acid sequences identified by sequence identification numbers 85, 94, 123-124, and 130; and (f) HVR-L3 includes HVRs with amino acid sequences from sequence identification numbers 95, 104, 125, and 131. In one embodiment, the present invention provides an antibody comprising at least one, at least two, or all three VH HVR sequences selected from (a) an amino acid sequence comprising any one of sequence identification numbers 45, 54, 117, and 126; (b) an amino acid sequence comprising any one of sequence identification numbers 55, 64, 118-120, and 127; and (c) an amino acid sequence comprising any one of sequence identification numbers 65, 74, 121, and 128. In one embodiment, the antibody comprises HVR-H3, which comprises an amino acid sequence comprising any one of sequence identification numbers 65, 74, 121, and 128. In another embodiment, the antibody comprises: HVR-H3, which includes an amino acid sequence of any one of sequence identification numbers: 65, 74, 121, 128; and HVR-L3, which includes an amino acid sequence of any one of sequence identification numbers: 95, 104, 125, 131. In yet another embodiment, the antibody comprises: HVR-H3, which includes an amino acid sequence of any one of sequence identification numbers: 65, 74, 121, 128; HVR-L3, which includes an amino acid sequence of any one of sequence identification numbers: 95, 104, 125, 131; and HVR-H2, which includes an amino acid sequence of any one of sequence identification numbers: 55, 64, 118-120, 127. In yet another embodiment, the antibody comprises (a) HVR-H1 comprising an amino acid sequence of any one of sequence identification numbers 45, 54, 117, and 126; (b) HVR-H2 comprising an amino acid sequence of any one of sequence identification numbers 55, 64, 118-120, and 127; and (c) HVR-H3 comprising an amino acid sequence of any one of sequence identification numbers 65, 74, 121, and 128. In another embodiment, the present invention provides an antibody comprising at least one, at least two, or all three VL HVR sequences selected from (a) an amino acid sequence comprising any one of sequence identification numbers 75, 84, 122, 129; (b) an amino acid sequence comprising any one of sequence identification numbers 85, 94, 123-124, 130; and (c) an amino acid sequence comprising any one of sequence identification numbers 95, 104, 125, 131. In one embodiment, the antibody includes (a) HVR-L1 comprising an amino acid sequence of any one of sequence identification numbers: 75, 84, 122, 129; (b) HVR-L2 comprising an amino acid sequence of any one of sequence identification numbers: 85, 94, 123-124, 130; and (c) HVR-L3 comprising an amino acid sequence of any one of sequence identification numbers: 95, 104, 125, 131. In another embodiment, the antibody of the present invention comprises (a) a VH domain comprising at least one, at least two, or all three VH HVR sequences selected from (i) an amino acid sequence comprising any one of sequence identification numbers 45, 54, 117, and 126; (ii) an amino acid sequence comprising any one of sequence identification numbers 55, 64, 118-120, and 127; and (iii) an amino acid sequence comprising any one of sequence identification numbers 65, 74, 121, and 128; and (b) a VL domain comprising at least one, at least two, or all three VH HVR sequences selected from (i) an amino acid sequence comprising any one of sequence identification numbers 75, 84, 122, and 129, comprising the amino acid sequence; (ii) an amino acid sequence comprising any one of sequence identification numbers 75, 84, 122, and 129; and (iii) an amino acid sequence comprising any one of sequence identification numbers 75, 84, 122, and 129; and (iv) an amino acid sequence comprising any one of sequence identification numbers 75, 84, 122, and 129; and (v ...iii) an amino acid sequence comprising any one of sequence identification numbers 75, 84, 122, and 129; and (viii) an amino acid sequence comprising any one of sequence identification numbers 75, 84, 122, and 129; and (viii) an amino acid sequence comprising any one of sequence identification numbers 75, 84, 122, HVR-L2 including any of the amino acid sequences in sequence identification numbers 85, 94, 123-124, and 130, and (c) VL HVR sequences of HVR-L3 including any of the amino acid sequences in sequence identification numbers 95, 104, 125, and 131. In another embodiment, the invention provides an antibody comprising: (a) HVR-H1 comprising an amino acid sequence of any one of sequence identification numbers 45, 54, 117, and 126; (b) HVR-H2 comprising an amino acid sequence of any one of sequence identification numbers 55, 64, 118-120, and 127; (c) HVR-H3 comprising an amino acid sequence of any one of sequence identification numbers 65, 74, 121, and 128; (d) HVR-L1 comprising an amino acid sequence of any one of sequence identification numbers 75, 84, 122, and 129; (e) HVR-L2 comprising an amino acid sequence of any one of sequence identification numbers 85, 94, 123-124, and 130; and (f) HVR-L3 comprising an amino acid sequence of any one of sequence identification numbers 95, 104, 125, and 131. In some specific embodiments, any one or more amino acids of the anti-C5 antibody provided above are substituted at the following HVR positions: (a) in HVR-H1 (Sequence Identification No.: 45), at positions 5 and 6; (b) in HVR-H2 (Sequence Identification No.: 55), at positions 1, 3, 9, 11, 13 and 15; (c) in HVR-H3 (Sequence Identification No.: 65), at positions 2, 5, 6, 12 and 13; (d) in HVR-L1 (Sequence Identification No.: 75), at positions 1, 5, 7 and 9; (e) in HVR-L2 (Sequence Identification No.: 85), at positions 4, 5 and 6; and (f) in HVR-L3 (Sequence Identification No.: 95), at positions 2, 4 and 12. In some specific embodiments, the substitutions are conservative substitutions, as provided herein. In some specific embodiments, any one or more of the following substitutions may be made in any combination: (a) in HVR-H1 (sequence identification number: 45), M5V or C6A; (b) in HVR-H2 (sequence identification number: 55), C1A or G, Y3F, T9D or E, Y11K or Q, S13D or E, or A15V; (c) in HVR-H3 (sequence identification number: 65), G2A, V5Q or D, T6Y, Y12H, or L13Y; (d) in HVR-L1 (sequence identification number: 75), Q1R, N5Q or G, G7S, D9K or S; (e) in HVR-L2 (sequence identification number: 85), K4T or E, L5T, or A6H, A6E, or A6Q; (f) In HVR-L3 (sequence identification number: 95), C2S, C2N, or C2T, F4K; or A12T or A12H. All possible combinations of the above substitutions are covered by the sequence identification numbers 126, 127, 128, 129, 130 and 131 of the common sequences of HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2 and HVR-L3 respectively. In any of the above embodiments, the anti-C5 antibody is humanized. In one embodiment, the anti-C5 antibody includes the HVR as in any of the above embodiments, and further includes a receptor human framework, such as a human immunoglobulin framework or a human common framework. In another embodiment, the anti-C5 antibody includes the HVR as in any of the above embodiments, and further includes VH or VL, which includes FR sequences, wherein the FR sequences are as follows: For the heavy chain variable domain, FR1 includes any amino acid sequence with sequence identification numbers 132 to 134, FR2 includes any amino acid sequence with sequence identification numbers 135 to 136, FR3 includes any amino acid sequence with sequence identification numbers 137 to 139, and FR4 includes any amino acid sequence with sequence identification numbers 140 to 141. For the light chain variable domain, FR1 includes any amino acid sequence of sequence identification number 142 to 143, FR2 includes any amino acid sequence of sequence identification number 144 to 145, FR3 includes any amino acid sequence of sequence identification number 146 to 147, and FR4 includes the amino acid sequence of sequence identification number 148. In another embodiment, the primary anti-C5 antibody includes a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to any of the amino acid sequences in sequence identification numbers 1 to 10. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity comprises substitutions (e.g., conserved substitutions), insertions, or deletions relative to a reference sequence, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in any of sequence identification numbers 1 to 10 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes a VH sequence from sequence identifiers 1 to 10, which contains a post-translational modification of that sequence. In a particular embodiment, the VH includes one, two, or three HVRs selected from: (a) HVR-H1 comprising an amino acid sequence from sequence identifiers 45 to 54, (b) HVR-H2 comprising an amino acid sequence from sequence identifiers 55 to 64, and (c) HVR-H3 comprising an amino acid sequence from sequence identifiers 65 to 74. The post-translational modification includes, but is not limited to, modifying the N-terminus of the heavy or light chain glutamic acid to pyroglutamic acid via pyroglutamylation. In another embodiment, an anti-C5 antibody is provided, wherein the antibody includes a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to any of the amino acid sequences in sequence identification numbers 11 to 20. In some specific embodiments, the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity comprises substitutions (e.g., conserved substitutions), insertions, or deletions relative to a reference sequence, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in any of sequence identification numbers 11 to 20 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes a VL sequence of any one of sequence identification numbers 11 to 20, which contains a post-translational modification of that sequence. In a particular embodiment, the VL includes one, two, or three HVRs selected from: (a) HVR-L1 comprising an amino acid sequence of any one of sequence identification numbers 75 to 84, (b) HVR-L2 comprising an amino acid sequence of any one of sequence identification numbers 85 to 94, and (c) HVR-L3 comprising an amino acid sequence of any one of sequence identification numbers 95 to 104. Post-translational modification includes, but is not limited to, modifying the N-terminus of the heavy or light chain of glutamic acid by pyroglutamylation to pyroglutamic acid. In another embodiment, a primary anti-C5 antibody is provided, wherein the antibody comprises VH as in any of the embodiments provided above, and VL as in any of the embodiments provided above. In one embodiment, the antibody comprises a VH sequence at any of sequence identification numbers 1 to 10 and a VL sequence at any of sequence identification numbers 11 to 20, respectively, comprising post-translational modifications of those sequences. Post-translational modification includes, but is not limited to, modification of the glutamic acid or glutamate at the N-terminus of the heavy or light chain to pyroglutamic acid via pyroglutamylation. In another embodiment, the primary anti-C5 antibody includes a heavy chain variable domain (VH) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to any of the amino acid sequences at sequence identification numbers 10, 106, to 110. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity comprises substitutions (e.g., conserved substitutions), insertions, or deletions relative to a reference sequence, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in any of sequence identification numbers 10, 106, to 110 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes a VH sequence from any of sequence identification numbers 10, 106 to 110, which contains a post-translational modification of that sequence. In a particular embodiment, the VH includes one, two, or three HVRs selected from: (a) HVR-H1 comprising an amino acid sequence from any of sequence identification numbers 45, 54, 117, and 126; (b) HVR-H2 comprising an amino acid sequence from any of sequence identification numbers 55, 64, 118-120, and 127; and (c) HVR-H3 comprising an amino acid sequence from any of sequence identification numbers 65, 74, 121, and 128. Post-translational modification includes, but is not limited to, pyroglutamylation modification of the N-terminus of the heavy or light chain of glutamic acid to pyroglutamic acid. In another embodiment, the primary anti-C5 antibody includes a VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to any of the amino acid sequences at sequence identification numbers 10, 106, to 110. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity comprises substitutions (e.g., conserved substitutions), insertions, or deletions relative to a reference sequence, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in any of sequence identification numbers 10, 106, to 110 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes a VH sequence from any of sequence identification numbers 10, 106 to 110, which contains a post-translational modification of that sequence. In a particular embodiment, the VH includes one, two, or three HVRs selected from: (a) HVR-H1 comprising an amino acid sequence from any of sequence identification numbers 45, 54, 117, and 126; (b) HVR-H2 comprising an amino acid sequence from any of sequence identification numbers 55, 64, 118-120, and 127; and (c) HVR-H3 comprising an amino acid sequence from any of sequence identification numbers 65, 74, 121, and 128. Post-translational modification includes, but is not limited to, pyroglutamylation modification of the N-terminus of the heavy or light chain of glutamic acid to pyroglutamic acid. In another embodiment, the primary anti-C5 antibody includes a VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to the amino acid sequence of sequence identification number 10. In some specific embodiments, the VH sequence is the amino acid sequence of sequence identification number 10. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with respect to the reference sequence includes substitutions (e.g., conserved substitutions), insertions, or deletions, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in sequence identification number 10 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes the VH sequence at sequence identification number 10, which contains a post-translational modification of that sequence. In a particular embodiment, the VH includes one, two, or three HVRs selected from: (a) HVR-H1 comprising the amino acid sequence at sequence identification number 54, (b) HVR-H2 comprising the amino acid sequence at sequence identification number 64, and (c) HVR-H3 comprising the amino acid sequence at sequence identification number 74. The post-translational modification includes, but is not limited to, modifying the N-terminus of the heavy or light chain glutamic acid to pyroglutamic acid via pyroglutamylation. In another embodiment, the primary anti-C5 antibody includes a VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to the amino acid sequence of sequence identification number 106. In some specific embodiments, the VH sequence is the amino acid sequence of sequence identification number 106. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with respect to the reference sequence comprises substitutions (e.g., conserved substitutions), insertions, or deletions, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in sequence identification number 106 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes the VH sequence at sequence identification number 106, which contains a post-translational modification of that sequence. In a particular embodiment, the VH includes one, two, or three HVRs selected from: (a) HVR-H1 comprising the amino acid sequence at sequence identification number 117, (b) HVR-H2 comprising the amino acid sequence at sequence identification number 118, and (c) HVR-H3 comprising the amino acid sequence at sequence identification number 121. The post-translational modification includes, but is not limited to, modifying the N-terminus of the heavy or light chain of glutamic acid by pyroglutamylation to pyroglutamic acid. In another embodiment, the primary anti-C5 antibody includes a VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to the amino acid sequence of sequence identification number 107. In some specific embodiments, the VH sequence is the amino acid sequence of sequence identification number 107. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with respect to the reference sequence includes substitutions (e.g., conserved substitutions), insertions, or deletions, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in sequence identification number 107 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes the VH sequence at sequence identification number 107, which contains a post-translational modification of that sequence. In a particular embodiment, the VH includes one, two, or three HVRs selected from: (a) HVR-H1 comprising the amino acid sequence at sequence identification number 117, (b) HVR-H2 comprising the amino acid sequence at sequence identification number 119, and (c) HVR-H3 comprising the amino acid sequence at sequence identification number 121. The post-translational modification includes, but is not limited to, modifying the N-terminus of the heavy or light chain of glutamic acid by pyroglutamylation to pyroglutamic acid. In another embodiment, the primary anti-C5 antibody includes a VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to the amino acid sequence of sequence identification number 108. In some specific embodiments, the VH sequence is the amino acid sequence of sequence identification number 108. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with respect to the reference sequence includes substitutions (e.g., conserved substitutions), insertions, or deletions, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in sequence identification number 108 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes the VH sequence at sequence identification number 108, which contains a post-translational modification of that sequence. In a particular embodiment, the VH includes one, two, or three HVRs selected from: (a) HVR-H1 comprising the amino acid sequence at sequence identification number 117, (b) HVR-H2 comprising the amino acid sequence at sequence identification number 118, and (c) HVR-H3 comprising the amino acid sequence at sequence identification number 121. The post-translational modification includes, but is not limited to, modifying the N-terminus of the heavy or light chain of glutamic acid by pyroglutamylation to pyroglutamic acid. In another embodiment, the primary anti-C5 antibody includes a VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to the amino acid sequence of sequence identification number 109. In some specific embodiments, the VH sequence is the amino acid sequence of sequence identification number 109. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with respect to the reference sequence includes substitutions (e.g., conserved substitutions), insertions, or deletions, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in sequence identification number 109 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes the VH sequence at sequence identification number 109, which contains a post-translational modification of that sequence. In a particular embodiment, the VH includes one, two, or three HVRs selected from: (a) HVR-H1 comprising the amino acid sequence at sequence identification number 117, (b) HVR-H2 comprising the amino acid sequence at sequence identification number 118, and (c) HVR-H3 comprising the amino acid sequence at sequence identification number 121. The post-translational modification includes, but is not limited to, modifying the N-terminus of the heavy or light chain of glutamic acid by pyroglutamylation to pyroglutamic acid. In another embodiment, the primary anti-C5 antibody includes a VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to the amino acid sequence of sequence identification number 110. In some specific embodiments, the VH sequence is the amino acid sequence of sequence identification number 110. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with respect to the reference sequence includes substitutions (e.g., conserved substitutions), insertions, or deletions, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in sequence identification number 110 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes the VH sequence at sequence identification number 110, which contains a post-translational modification of that sequence. In a particular embodiment, the VH includes one, two, or three HVRs selected from: (a) HVR-H1 comprising the amino acid sequence at sequence identification number 117, (b) HVR-H2 comprising the amino acid sequence at sequence identification number 120, and (c) HVR-H3 comprising the amino acid sequence at sequence identification number 121. The post-translational modification includes, but is not limited to, modifying the N-terminus of the heavy or light chain of glutamic acid by pyroglutamylation to pyroglutamic acid. In another embodiment, an anti-C5 antibody is provided, wherein the antibody includes a light chain variable domain (VL) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any of the amino acid sequences in sequence identification numbers 20, 111-113. In some specific embodiments, the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity comprises substitutions (e.g., conserved substitutions), insertions, or deletions relative to a reference sequence, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in any of sequence identification numbers 20, 111-113 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes a VL sequence from any of sequence identification numbers 20, 111-113, which contains a post-translational modification of that sequence. In a particular embodiment, the VL includes one, two, or three HVRs selected from: (a) HVR-L1 comprising an amino acid sequence from any of sequence identification numbers 75, 84, 122, 129; (b) HVR-L2 comprising an amino acid sequence from any of sequence identification numbers 85, 94, 123-124, 130; and (c) HVR-L3 comprising an amino acid sequence from any of sequence identification numbers 95, 104, 125, 131. Post-translational modification includes, but is not limited to, pyroglutamylation modification of the N-terminus of the heavy or light chain of glutamic acid to pyroglutamic acid. In another embodiment, an anti-C5 antibody is provided, wherein the antibody comprises a VL having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to the amino acid sequence of Sequence Identification Number: 20. In some specific embodiments, the VL sequence is the amino acid sequence of Sequence Identification Number: 20. In some specific embodiments, the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with respect to the reference sequence comprises substitutions (e.g., conserved substitutions), insertions, or deletions, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in Sequence Identification Number: 20 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes the VL sequence at sequence identification number 20, which contains a post-translational modification of that sequence. In a particular embodiment, the VL includes one, two, or three HVRs selected from: (a) HVR-L1 comprising the amino acid sequence at sequence identification number 84, (b) HVR-L2 comprising the amino acid sequence at sequence identification number 94, and (c) HVR-L3 comprising the amino acid sequence at sequence identification number 104. Post-translational modification includes, but is not limited to, pyroglutamylation of the glutamic acid or glutamine at the N-terminus of the heavy or light chain to pyroglutamic acid. In another embodiment, an anti-C5 antibody is provided, wherein the antibody comprises a VL having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to the amino acid sequence of sequence identification number 111. In some specific embodiments, the VL sequence is the amino acid sequence of sequence identification number 111. In some specific embodiments, the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with respect to the reference sequence comprises substitutions (e.g., conserved substitutions), insertions, or deletions, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in sequence identification number 111 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes the VL sequence at sequence identification number 111, which contains a post-translational modification of that sequence. In a particular embodiment, the VL includes one, two, or three HVRs selected from: (a) HVR-L1 comprising the amino acid sequence at sequence identification number 122, (b) HVR-L2 comprising the amino acid sequence at sequence identification number 123, and (c) HVR-L3 comprising the amino acid sequence at sequence identification number 125. The post-translational modification includes, but is not limited to, modifying the N-terminus of the heavy or light chain glutamic acid to pyroglutamic acid via pyroglutamylation. In another embodiment, an anti-C5 antibody is provided, wherein the antibody comprises a VL having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to the amino acid sequence of sequence identification number: 112. In some specific embodiments, the VL sequence is the amino acid sequence of sequence identification number: 112. In some specific embodiments, the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with respect to the reference sequence comprises substitutions (e.g., conserved substitutions), insertions, or deletions, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in sequence identification number: 112 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes the VL sequence at sequence identification number 112, which contains a post-translational modification of that sequence. In a particular embodiment, the VL includes one, two, or three HVRs selected from: (a) HVR-L1 comprising the amino acid sequence at sequence identification number 122, (b) HVR-L2 comprising the amino acid sequence at sequence identification number 123, and (c) HVR-L3 comprising the amino acid sequence at sequence identification number 125. Post-translational modification includes, but is not limited to, modifying the N-terminus of the heavy or light chain of glutamic acid by pyroglutamylation to pyroglutamic acid. In another embodiment, an anti-C5 antibody is provided, wherein the antibody comprises a VL having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with respect to the amino acid sequence of sequence identification number: 113. In some specific embodiments, the VL sequence is the amino acid sequence of sequence identification number: 113. In some specific embodiments, the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with respect to the reference sequence comprises substitutions (e.g., conserved substitutions), insertions, or deletions, but the anti-C5 antibody including that sequence retains the ability to bind to C5. In some specific embodiments, a total of 1 to 10 amino acids in sequence identification number: 113 are substituted, inserted, and / or deleted. In some specific embodiments, the substitution, insertion, or deletion occurs in a region outside the HVR (i.e., in the FR). Optionally, the anti-C5 antibody includes the VL sequence at sequence identification number 113, which contains a post-translational modification of that sequence. In a particular embodiment, the VL includes one, two, or three HVRs selected from: (a) HVR-L1 comprising the amino acid sequence at sequence identification number 122, (b) HVR-L2 comprising the amino acid sequence at sequence identification number 124, and (c) HVR-L3 comprising the amino acid sequence at sequence identification number 125. Post-translational modification includes, but is not limited to, modifying the N-terminus of the heavy or light chain glutamic acid to pyroglutamic acid via pyroglutamylation. In another embodiment, a primary antibody against C5 is provided, wherein the antibody includes the VH sequence as described in any of the embodiments provided above, and the VL sequence as described in any of the embodiments provided above. In one embodiment, the antibody includes a VH sequence at any of sequence identification numbers 10, 106 to 110 and a VL sequence at any of sequence identification numbers 20, 111 to 113, comprising post-translational modifications of those sequences. Post-translational modification includes, but is not limited to, modification of the N-terminus of the heavy or light chain of glutamic acid to pyroglutamic acid by pyroglutamylation. In one embodiment, the antibody includes the VH sequence at sequence identification number 10 and the VL sequence at sequence identification number 20. In one embodiment, the antibody includes the VH sequence at sequence identification number 106 and the VL sequence at sequence identification number 111. In another embodiment, the antibody includes a VH sequence of sequence identification number 107 and a VL sequence of sequence identification number 111. In yet another embodiment, the antibody includes a VH sequence of sequence identification number 108 and a VL sequence of sequence identification number 111. In another embodiment, the antibody includes a VH sequence of sequence identification number 109 and a VL sequence of sequence identification number 111. In another embodiment, the antibody includes a VH sequence of sequence identification number 109 and a VL sequence of sequence identification number 112. In another embodiment, the antibody includes a VH sequence of sequence identification number 109 and a VL sequence of sequence identification number 113. In yet another embodiment, the antibody includes a VH sequence of sequence identification number 110 and a VL sequence of sequence identification number 113. In one state, a primary anti-C5 antibody is provided, wherein the antibody comprises a VH sequence comprising (a) HVR-H1 comprising an amino acid sequence of sequence identification number 54, (b) HVR-H2 comprising an amino acid sequence of sequence identification number 64, and (c) HVR-H3 comprising an amino acid sequence of sequence identification number 74, and a VL sequence comprising (a) HVR-L1 comprising an amino acid sequence of sequence identification number 84; (b) HVR-L2 comprising an amino acid sequence of sequence identification number 94; and (c) HVR-L3 comprising an amino acid sequence of sequence identification number 104. In another sample, a primary antibody against C5 is provided, wherein the antibody comprises a VH sequence comprising (a) HVR-H1 comprising an amino acid sequence of sequence identification number 117, (b) HVR-H2 comprising an amino acid sequence of sequence identification number 118, and (c) HVR-H3 comprising an amino acid sequence of sequence identification number 121, and a VL sequence comprising (a) HVR-L1 comprising an amino acid sequence of sequence identification number 122; (b) HVR-L2 comprising an amino acid sequence of sequence identification number 123; and (c) HVR-L3 comprising an amino acid sequence of sequence identification number 125. In another sample, a primary antibody against C5 is provided, wherein the antibody comprises a VH sequence comprising (a) HVR-H1 comprising an amino acid sequence of sequence identification number 117, (b) HVR-H2 comprising an amino acid sequence of sequence identification number 119, and (c) HVR-H3 comprising an amino acid sequence of sequence identification number 121, and a VL sequence comprising (a) HVR-L1 comprising an amino acid sequence of sequence identification number 122; (b) HVR-L2 comprising an amino acid sequence of sequence identification number 123; and (c) HVR-L3 comprising an amino acid sequence of sequence identification number 125. In another sample, a primary anti-C5 antibody is provided, wherein the antibody comprises a VH sequence comprising (a) HVR-H1 comprising an amino acid sequence of sequence identification number 117, (b) HVR-H2 comprising an amino acid sequence of sequence identification number 118, and (c) HVR-H3 comprising an amino acid sequence of sequence identification number 121, and a VL sequence comprising (a) HVR-L1 comprising an amino acid sequence of sequence identification number 122; (b) HVR-L2 comprising an amino acid sequence of sequence identification number 124; and (c) HVR-L3 comprising an amino acid sequence of sequence identification number 125. In another sample, a primary antibody against C5 is provided, wherein the antibody comprises a VH sequence comprising (a) HVR-H1 comprising an amino acid sequence of sequence identification number 117, (b) HVR-H2 comprising an amino acid sequence of sequence identification number 120, and (c) HVR-H3 comprising an amino acid sequence of sequence identification number 121, and a VL sequence comprising (a) HVR-L1 comprising an amino acid sequence of sequence identification number 122; (b) HVR-L2 comprising an amino acid sequence of sequence identification number 124; and (c) HVR-L3 comprising an amino acid sequence of sequence identification number 125. In some specific embodiments, the anti-C5 antibody of the present invention includes the VH region as described in any of the embodiments provided above, and a heavy chain constant region including an amino acid sequence of any one of sequence identification numbers 33, 34, 35, 114, 115, and 116. In some specific embodiments, the anti-C5 antibody of the present invention includes the VL region as described in any of the embodiments provided above, and a light chain constant region including an amino acid sequence of any one of sequence identification numbers 36, 37, and 38. In another embodiment, the present invention provides an antibody that binds to the same antigenic determinant as the anti-C5 antibody provided herein. For example, in some specific embodiments, the provided antibody binds to the same antigenic determinant as the antibodies described in Table 2. As shown in the operational examples below, all the anti-C5 antibodies described in Table 2 are categorized into the same antigenic determinant compartment for C5 and exhibit pH-dependent binding properties. In yet another embodiment, the present invention provides an antibody that binds to the same antigenic determinant as the antibodies provided herein. In yet another embodiment, the present invention provides an antibody that binds to the same antigenic determinant as the antibodies described in Table 7 or 8. In some specific embodiments, an antibody is provided that binds to an antigenic determinant within a fragment consisting of amino acids 33 to 124 of the β chain of C5 (Sequence Identification Number: 40). In some specific embodiments, an antibody is provided that binds to an antigenic determinant within the β chain of C5 (Sequence Identification Number: 40), comprising at least one fragment selected from the group consisting of amino acids 47-57, 70-76, and 107-110. In some specific embodiments, an antibody is provided that binds to an antigenic determinant within a fragment of the β chain (sequence identification number: 40) of C5, comprising at least one amino acid selected from the group consisting of Thr47, Glu48, Ala49, Phe50, Asp51, Ala52, Thr53, Lys57, His70, Val71, His72, Ser74, Glu76, Val107, Ser108, ​​Lys109, and His110. In another embodiment, the antigenic determinant of the anti-C5 antibody of the present invention is a conformational antigenic determinant. In another embodiment, the anti-C5 antibody according to any of the above embodiments is a monoclonal antibody, comprising chimeric, humanized, or human antibodies. In one embodiment, the anti-C5 antibody is an antibody fragment, such as Fv, Fab, Fab', scFv, diabody, or F(ab'). 2. In another embodiment, the antibody is a full-length antibody, such as a complete IgG1 or IgG4 antibody or other antibody species or isotypes as defined herein. In another variant, the anti-C5 antibody according to any of the above embodiments may combine any feature, either alone or in combination, as described in sections 1-7 below: 1. Antibody affinity In some specific embodiments, the antibodies provided herein have ≤1 µm, ≤100 nM, ≤10 nM, ≤1 nM, ≤0.1 nM, ≤0.01 nM, or ≤0.001 nM (e.g., 10 µm). -8 M or smaller, for example from 10 -8 M to 10 -13 M, for example, from 10 -9 M to 10 -13 The dissociation constant (Kd) of M). In one embodiment, Kd is measured using a radiolabeled antigen binding assay (RIA). In one embodiment, the RIA is performed in Fab form of the antibody of interest and its antigen. For example, by using the minimum concentration of ( ) under conditions of a titration series in the presence of unlabeled antigen. 125 I) Labeling antigens to balance Fab, then capturing bound antigens with a disc coated with anti-Fab antibody to measure the solution-binding affinity of Fab to the antigen (see, for example, Chen et al.). J. Mol. Biol. 293:865-881 (1999)). To establish the assay conditions, 5 μg / ml of capture MICROTITER (cappel Labs) was used in 50 mM sodium carbonate (pH 9.6). ® Incubate overnight in a multi-well plate (Thermo Scientific), followed by blockade with 2% (w / v) bovine serum albumin in PBS at room temperature (approximately 23°C) for 2 to 5 hours. In a non-adsorbent plate (Nunc#269620), add 100 pM or 26 pM [ 125 I]-Antigens and serially diluted Fabs of interest (e.g., with Presta et al., The mixture was then mixed with anti-VEGF antibodies (as described in Cancer Res. 57:4593-4599 (1997), consistent with the assessment of Fab-12). The Fab of interest was then incubated overnight; however, incubation can continue for a longer period (e.g., approximately 65 hours) to ensure equilibrium is reached. Afterward, the mixture was transferred to a trap and incubated at room temperature (e.g., 1 hour). The solution was then removed and mixed with a solution containing 0.1% polysorbate 20 (TWEEN-20). ® Wash the trays 8 times with PBS. Once the trays are dry, add 150 μl / well of scintillation buffer (MICROSCINT-20). TM Packard), and at TOPCOUNT TM Count the disks for 10 minutes using a gamma counter (Packard). Select each Fab to give a concentration less than or equal to 20% of the maximum binding for the competitive binding assay. According to another embodiment, Kd utilizes BIACORE. ® Measurements were performed using surface plasma resonance methods. For example, BIACORE was used. ® -2000 or BIACORE ® -3000 (BIACORE ® The assay method of Piscataway, Inc. (NJ) is performed at 25°C using an immobilized antigen CM5 wafer at approximately 10 response units (RU). In one embodiment, according to the supplier's instructions, the assay method is performed using... N-ethyl- N'-(3-Dimethylaminopropyl)-carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) activated carboxymethylated polydextrose biosensor chip (CM5, BIACORE) ® Before injecting the conjugate protein at a flow rate of 5 μl / min to obtain approximately 10 response units (RU), the antigen was diluted to 5 μg / ml (approximately 0.2 μM) with 10 mM sodium acetate, pH 4.8. Following antigen injection, 1 M ethanolamine was injected to block unreacted groups. For kinetic measurements, serially diluted Fab (0.78 nM to 500 nM) was injected at approximately 25 μl / min at 25 °C into a solution containing 0.05% polysorbate 20 (TWEEN-20). TMInteractive agents in PBS (PBST). A simple one-to-one Langmuir binding model (BIACORE) was used. ® Evaluation Software version 3.2 calculates the binding rate (k) by simultaneously fitting binding and dissociation sensor maps. on ) and dissociation rate (k off The equilibrium dissociation constant (Kd) is proportional to k. off / k on Calculations. Please refer to, for example, Chen et al. J. Mol. Biol. 293:865-881 (1999). If, according to the above surface plasma resonance determination method, the binding rate exceeds 10... 6 M -1 s -1 The binding rate was determined using fluorescence quenching technology. It was measured at 25°C in PBS, pH 7.2, by the increase or decrease in the fluorescence emission intensity (excitation = 295 nm; emission = 340 nm, 16 nm bandpass) of 20 nM anti-antigen antibody (Fab form). This was measured on a spectrometer, such as an Aviv Instruments spectrophotometer equipped with a stop-flow device or an 8000 series SLM-AMINCO spectrophotometer with stirring tubes. TM A spectrophotometer (ThermoSpectronic) is used to measure the concentration of antigen in the presence of an increase. 2. Antibody fragments. In some specific embodiments, the antibodies provided herein are antibody fragments. Antibody fragments include, but are not limited to, Fab, Fab', Fab'-SH, and F(ab'). 2. Fv and scFv fragments, and other fragments as described below. For a review of specific antibody fragments, please refer to Hudson et al. Nat. Med. 9:129-134 (2003). For reviews of specific scFv fragments, please refer to, for example, Pluckthün, in The Pharmacology of Monoclonal Antibodies, vol. 113, edited by Rosenburg and Moore (Springer-Verlag, New York), pp. 269-315 (1994); see also WO 93 / 16185; and U.S. Patent Nos. 5,571,894 and 5,587,458. [The text then abruptly shifts to a seemingly unrelated topic:] ...including salvage receptors binding antigenic determinant residues and having increased in vivo (... (in vivo) Fab and F(ab') during the half-life period For a discussion of the two segments, please refer to U.S. Patent No. 5,869,046. A diobody is an antibody fragment with two antigen-binding sites. It can be bivalent or bispecific; see, for example, EP 404,097; WO 1993 / 01161; Hudson et al. Nat. Med. 9:129-134 (2003); and Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993). Tri-antibodies and tetra-antibodies are also described in Hudson et al. Nat. Med. 9:129-134 (2003). A single-domain antibody is an antibody fragment comprising all or part of the heavy chain variable domain or all or part of the light chain variable domain of an antibody. In some specific embodiments, the single-domain antibody is a human single-domain antibody (Domantis, Inc., Waltham, MA; see, for example, U.S. Patent No. 6,248,516B1). Antibody fragments can be formed using a variety of techniques, including but not limited to the proteolytic digestion of intact antibodies, and by recombining host cells (e.g., The production of E. coli (or bacteriophages), as described in this article. 3. Chimeric and humanized antibodies. In some specific embodiments, the antibodies provided herein are chimeric antibodies. Specific chimeric antibodies are described, for example, in U.S. Patent No. 4,816,567; and in Morrison et al. Proc. Natl. Acad. Sci. USA 81:6851-6855 (1984)). In one example, a chimeric antibody includes a non-human variable region (e.g., a variable region derived from mice, rats, rodents, rabbits, or non-human primates, such as monkeys) and a human constant region. In yet another example, a chimeric antibody is a "class-switched" antibody, where the class or subclass has been changed from that of the parent antibody. Chimeric antibodies contain their antigen-binding fragment. In some specific embodiments, the chimeric antibody is a humanized antibody. Typically, non-human antibodies are humanized to reduce their immunogenicity to humans while retaining the specificity and affinity of the parent non-human antibody. Generally, humanized antibodies include one or more variable domains, wherein the HVR, for example, the CDR (or a portion thereof) is derived from the non-human antibody, and the FR (or a portion thereof) is derived from the human antibody sequence. Humanized antibodies may also optionally include at least a portion of the human constant region. In some embodiments, some FR residues in the humanized antibody are replaced by corresponding residues from the non-human antibody (e.g., the antibody from which the HVR residues are derived), for example, to restore or improve antibody specificity or affinity. A review of humanized antibodies and their preparation methods can be found in, for example, Almagro and Fransson. Front. Biosci. 13:1619-1633 (2008), and further described, for example, by Riechmann et al. Nature 332:323-329 (1988); Queen et al. Proc. Nat'l Acad. Sci. USA 86:10029-10033 (1989); US Patent Nos. 5,821,337, 7,527,791, 6,982,321 and 7,087,409; Kashmiri et al. Methods 36:25-34 (2005) (Description of Specificity Determination Region (SDR) shift); Padlan, Mol. Immunol. 28:489-498 (1991) (description of "surface rework"); Dall'Acqua et al., Methods 36:43-60 (2005) (describes “FR reorganization”); and Osbourn et al., Methods 36:61-68 (2005) and Klimka et al., Br. J. Cancer 83:252-260 (2000) (Describes the “guided selection” approach for FR reorganization). Human frame regions that can be used for humanization include, but are not limited to: frame regions selected using an "optimal" method (see, for example, Sims et al.). J. Immunol. 151:2296 (1993); Frame regions of common sequences of human antibodies derived from specific subtypes of light or heavy chain variable regions (see, for example, Carter et al.). Proc. Natl. Acad. Sci. USA89:4285 (1992); and Presta et al., J. Immunol. 151:2623 (1993); Human mature (somatic mutation) framework region or human germline framework region (see, for example, Almagro and Fransson, Front. Biosci. 13:1619-1633 (2008)); and the frame region derived from screening FR databases (see, for example, Baca et al., J. Biol. Chem. 272:10678-10684 (1997) and Rosok et al., J. Biol. Chem. 271:22611-22618 (1996)). 4. Human antibodies In some specific embodiments, the antibodies provided herein are human antibodies. Human antibodies can be manufactured using various known techniques. Human antibodies are broadly described in van Dijk and van de Winkel. Curr. Opin. Pharma. 5:368-74 (2001) and Lonberg, Curr. Opin. Immunol. 20:450-459 (2008). Human antibodies can be prepared by administering an immunogen to genetically modified transgenic animals that produce complete human antibodies in response to antigen attack, or complete antibodies with human variable regions. These animals typically contain all or part of the human immunoglobulin loci, which replace endogenous immunoglobulin loci, or are located extrachromosomally or randomly integrated into the animal's chromosome. In these transgenic mice, endogenous immunoglobulin loci are generally inactive. For a review of methods for obtaining human antibodies from transgenic animals, please refer to Lonberg. Nat. Biotech. 23:1117-1125 (2005). Also see, for example, U.S. Patent Nos. 6,075,181 and 6,150,584, which describe XENOMOUSE. TM The technologies described are: U.S. Patent No. 5,770,429, which describes HuMab® technology; U.S. Patent No. 7,041,870, which describes KM MOUSE® technology; and U.S. Patent Publication No. US 2007 / 0061900, which describes VelociMouse® technology. The human variable region of the complete antibody produced by these animals can be further modified, for example, by combining it with different human constant regions. Human antibodies can also be generated using fusion-tumor-based methods. Human myeloma and mouse-human fusion myeloma cell lines used for generating human monoclonal antibodies have been described. (See, for example, Kozbor, ...) J. Immunol. 133:3001 (1984); Brodeur et al. Monoclonal antibody production techniques and applications, pp. 51-63 (Dekker, Inc., New York, 1987); and Boerner et al., J. Immunol. 147:86 (1991). Human antibodies produced using human B-cell fusion tumor technology have also been used by Li et al. Proc. Natl. Acad. Sci. USA 103:3557-3562 (2006). Other methods include those described in, for example, U.S. Patent No. 7,189,826 (describes the production of monoclonal human IgM antibodies from fusion tumor cell lines) and Ni, Xiandai Mianyixue 26(4):265-268 (2006) (Description of methods for human-to-human fusion tumors). Human fusion tumor technology (Trioma technology) is also described in Vollmers. Histology and Histopathology20(3):927-937 (2005) and Vollmers, Methods and Findings in Experimental and Clinical Pharmacology27(3):185-191 (2005). Human antibodies can also be generated by isolating variable domain sequences from Fv strains derived from human phage display databases. These variable domain sequences can then be combined with desired human constant domains. The technique for selecting human antibodies from antibody databases is described below. 5. Antibodies derived from databases The antibodies of the present invention can be isolated by screening for antibodies with the desired activity in a combinatorial library. For example, various methods for generating phage display libraries and screening for antibodies with the desired binding characteristics in such libraries are known in the art. Such methods are summarized, for example, by Hoogenboom et al. Methods in Molecular Biology 178:1-37 (edited by O'Brien et al., Human Press, Totowa, NJ, 2001), and further, for example, McCafferty et al., Nature 348:552-554; Clackson et al., Nature 352:624-628 (1991); Marks et al. J. Mol. Biol.222:581-597 (1992); Marks, Meth.Mol. Biol. 248:161-175 (Lo, ed., Human Press, Totowa, NJ, 2003); Sidhu et al. J. Mol. Biol. 338(2):299-310 (2004); Lee et al. J. Mol. Biol. 340(5):1073-1093 (2004); Fellouse, Proc. Natl. Acad. Sci. USA 101(34):12467-12472 (2004); Lee et al. As described in J. Immunol. Methods284(1-2):119-132 (2004). In specific phage display methods, the repertoires of the VH and VL genes are selected and randomly recombined into a phage database using polymerase chain reaction (PCR), and then, as in the case of Winter et al., The screening of antigen-binding phages described in Ann. Rev. Immunol. 12:433-455 (1994) is performed. Phages typically present antibody fragments in the form of single-chain Fv (ScFv) fragments or Fab fragments. Libraries derived from immune sources can provide high-affinity antibodies against immunogens without the need for fusion tumor construction. Alternatively, natural libraries can be cloned (e.g., from humans) to provide a single source of antibodies against a broad range of non-autoantigens and autoantigens in the absence of any immunization, as described by Griffiths et al. As described in EMBO J,12:725-734 (1993). Finally, it is also possible to encode the highly variable CDR3 region by transfecting the unrearranged V gene fragment from stem cells and using a PCR primer containing a random sequence, and to achieve in vitro ( In vitro rearrangements are used to synthetically generate natural libraries, such as Hoogenboom. J. Mol. Biol. 227:381-388 (1992). Patent publications describing human antibody phage databases include, for example, U.S. Patent No. 5,750,373, and U.S. Patent Publications Nos. 2005 / 0079574, 2005 / 0119455, 2005 / 0266000, 2007 / 0117126, 2007 / 0160598, 2007 / 0237764, 2007 / 0292936, and 2009 / 0002360. Antibodies or antibody fragments isolated from human antibody databases are considered human antibodies or human antibody fragments in this article. 6. Multispecific antibodies In some specific embodiments, the antibody provided is a multispecific antibody, such as a bispecific antibody. A multispecific antibody is a monoclonal antibody that has binding specificity to at least two different sites. In some specific embodiments, one of the binding specificities is against C5 and the other is against any other antigen. In some specific embodiments, a bispecific antibody may bind to two different antigenic determinants of C5. Bispecific antibodies can also be used to target cytotoxic agents to cells expressing C5. Bispecific antibodies can be formulated as full-length antibodies or antibody fragments. Techniques for manufacturing multispecific antibodies include, but are not limited to, recombinant co-expression of two immunoglobulin heavy-light chain pairs with different specificities (see Milstein and Cuello). Nature 305:537 (1983)), WO 93 / 08829, and Traunecker et al., EMBO J.10:3655 (1991) and “knob-in-hole” engineering (see, for example, US Patent No. 5,731,168). Multispecific antibodies can also be prepared by: engineering the electrostatic attraction of the Fc-heterodimer molecules used to prepare the antibody (WO 2009 / 089004A1); crosslinking two or more antibodies or fragments (see, for example, US Patent No. 4,676,980, and Brennan et al.). Science 229:81 (1985); using leucine zippers to generate bispecific antibodies (see, for example, Kostelny et al., J. Immunol. 148(5): 1547-1553 (1992)); using "double antibody" technology to generate bispecific antibody fragments (see, for example, Hollinger et al., Proc. Natl. Acad. Sci. USA90:6444-6448 (1993)); and the use of single-stranded Fv (scFv) dimers (see, for example, Gruber et al., J. Immunol. 152:5368 (1994)); and the preparation of trispecific antibodies, such as, for example, Tutt et al. As described in J. Immunol. 147:60 (1991). This article also includes engineered antibodies with three or more functional antigen-binding sites, including “octopus antibodies” (see, for example, US 2006 / 0025576). The antibodies or fragments described herein also contain "dual-acting FAbs" or "DAFs," which include antigen-binding sites to both C5 and another different antigen (see, for example, US 2008 / 0069820). 7. Antibody Variants In some specific embodiments, the amino acid sequence variants of the antibodies provided herein are contemplated. For example, enhancing the binding affinity and / or other biological properties of the antibody may be desirable. Amino acid sequence variants of the antibody can be prepared by introducing appropriate modifications to the nucleotide sequence encoding the antibody, or by peptide synthesis. Such modifications include, for example, deletion, and / or insertion and / or substitution of residues within the amino acid sequence of the antibody. Any combination of deletions, insertions, and substitutions can be achieved in the final construct, provided that the final construct possesses the desired characteristics, such as antigen binding. a. Substitution, Insertion, and Deletion Variants In some specific embodiments, antibody variants with one or more amino acid substitutions are provided. The sites of interest for substitution mutagenesis include HVR and FR. Conserved substitutions are shown under the heading "Preferred Substitutions" in Table 1. More substantial changes are provided under the heading "Exemplary Substitutions" in Table 1, and are further described below with reference to the amino acid side chain categories. Amino acid substitutions can be introduced into antibodies of interest and screened into products with desired activities, such as retained / improved antibody binding, reduced immunogenicity, or improved ADCC or CDC. Table 1 Amino acids can be classified according to their common side chain characteristics as follows: (1) hydrophobic: leucine, Met, Ala, Val, Leu, Ile; (2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues that affect chain orientation: Gly, Pro; and (6) aromatic: Trp, Tyr, Phe. Non-conservative substitution would result in members of one of these categories being swapped with members of another category. Substitution variants are a class of variants that involve replacing one or more highly variable residues in a parent antibody (e.g., a humanized or human antibody). Generally, the variants selected for further research will have modifications (e.g., improvements) in specific biological properties (e.g., increased affinity, decreased immunogenicity) relative to the parent antibody and / or will have substantially retained the specific biological properties of the parent antibody. Exemplary substitution variants are affinity-matured antibodies, which can be conveniently generated, for example, using affinity maturation techniques such as those described herein based on phage display. In short, one or more HVR residues are mutated and a variant antibody is displayed on a phage, followed by screening for specific biological activities (e.g., binding affinity). Modifications (e.g., substitutions) can be formed in HVRs to improve antibody affinity, for example. Such modifications can form in HVR “hotspots,” which are residues encoded by codons that undergo mutations at a high frequency during somatic maturation (see, for example, Chowdhury). Methods Mol. Biol. 207:179-196 (2008), and / or contacting the residues of the antigen, and testing the binding affinity of the obtained variants VH or VL. Affinity maturation by constructing and reselecting from a second database has been, for example, Hoogenboom et al. Methods in Molecular Biology 178:1-37 (O'Brien et al., ed., Human Press, Totowa, NJ, (2001)). In some embodiments of affinity maturation, diversity is introduced into the variant gene selected for maturation by any of a variety of methods (e.g., error-prone PCR, strand shuffling, or oligonucleotide directed mutagenesis). A second database is then generated. The database is then screened to identify any antibody variant with the desired affinity. Another method for introducing diversity involves HVR directed methods, in which several HVR residues (e.g., 4 to 6 residues at a time) are randomized. HVR residues involved in antigen binding can be specifically identified, for example, by alanine scanning mutagenesis or by modeling. CDR-H3 and CDR-L3 are particularly commonly targeted. In certain embodiments, substitution, insertion, or deletion may occur within one or more HVRs, provided that such modifications do not substantially reduce the antibody's ability to bind to the antigen. For example, conserved modifications that do not substantially reduce binding affinity (e.g., conserved substitutions as provided herein) may be formed in the HVR. Such modifications may, for example, be outside the antigen-contacting residues in the HVR. In the specific embodiments of the variant VH and VL sequences provided above, each HVR is either unmodified or contains no more than one, two, or three amino acid substitutions. A method that can be used to identify antibody residues or regions that can be targeted for mutagenesis is called "alanine scanning mutagenesis," as exemplified by Cunningham. As described in Science 244:1081-1085 (1989). In this method, a residue or group of residues (e.g., charged residues such as arg, asp, his, lys, and glu) can be identified and substituted with a neutral or negatively charged amino acid (e.g., alanine or polyalanine) to determine whether it affects the antibody-antigen interaction. Further substitutions can be introduced at amino acid sites that show functional sensitivity to the initial substitution. Alternatively, or additionally, the crystal structure of the antigen-antibody complex identifies contact points between the antibody and antigen. Such contact residues and adjacent residues can be targeted or eliminated as candidates for substitution. Variants can be screened to determine whether they contain the desired properties. Amino acid sequence inserts include amino- and / or carboxyl-terminal fusions of peptides ranging in length from one residue to 100 or more residues, as well as intra-sequence inserts of single or multiple amino acid residues. Examples of terminal inserts include antibodies having an N-terminal methionine residue. Other insertion variants of antibody molecules include fusions of the N- or C-terminus of the antibody with an enzyme (e.g., ADEPT) or peptide, which increase the serum half-life of the antibody. b. Glycosylation variants In some specific embodiments, the antibodies provided herein are modified to increase or decrease the degree of glycosylation. The addition or deletion of glycosylation sites on the antibody can be conveniently accomplished by modifying the amino acid sequence to create or remove one or more glycosylation sites. When an antibody includes an Fc region, the sugars attached to it can be modified. Naturally occurring antibodies produced by mammalian cells typically consist of branched, bitennary oligosaccharides, which are generally attached to the CH2 domain of the Fc region via an N-linked Asn297. See, for example, Wright et al. TIBTECH 15:26-32 (1997). Oligosaccharides may comprise various sugars, such as mannose, N-acetylglucosamine (GlcNAc), galactose, and sialic acid, as well as fucose of GlcNAc attached to the "backbone" of the bipolar oligosaccharide structure. In some embodiments, oligosaccharide formation modifications may be made in the antibodies of the present invention to produce antibody variants with specific improved properties. In one embodiment, the provided antibody variant has a glycosylation structure lacking fucose attached (directly or indirectly) to the Fc region. For example, the amount of fucose in such antibodies can be from 1% to 80%, from 1% to 65%, from 5% to 65%, or from 20% to 40%. The amount of fucose is determined by calculating the average amount of fucose within the Asn297 of the glycan chain relative to the sum of all glycosyl structures attached to Asn297 (e.g., complexes, hybrids, and high-mannose structures) as measured by MALDI-TOF mass spectrometry, for example, as described in WO 2008 / 077546. Asn297 refers to the aspartic acid residue located approximately at position 297 (Eu number of the Fc region residue) in the Fc region; however, due to minor sequence variations in antibodies, Asn297 can also be located approximately ±3 amino acids upstream or downstream of position 297, i.e., between positions 294 and 300. Such fucosylation variants can have improved ADCC function; see, for example, U.S. Patent Publication Nos. 2003 / 0157108 (Presta, L.); 2004 / 0093621 (Kyowa Hakko Kogyo Co., Ltd.). Examples of publicly available publications involving “defucosylated” or “fucose-deficient” antibody variants include: US 2003 / 0157108; WO 2000 / 61739; WO 2001 / 29246; US 2003 / 0115614; US 2002 / 0164328; US 2004 / 0093621; US ​​2004 / 0132140; US 2004 / 0110704; US 2004 / 0110282; US 2004 / 0109865; WO 2003 / 085119; WO 2003 / 084570; WO 2005 / 035586; WO 2005 / 035778; WO 2005 / 053742; WO 2002 / 031140; Okazaki et al., J. Mol. Biol. 336:1239-1249 (2004); Yamane-Ohnuki et al. Biotech. Bioeng. 87:614 (2004). Examples of cell lines capable of producing defucosylated antibodies include Lecl3 CHO cells lacking protein fucosylation (Ripka et al., Arch. Biochem. Biophys. 249:533-545 (1986); US 2003 / 0157108, Presta, L; and WO 2004 / 056312, Adams et al., particularly in Example 11), and knockout cell lines, such as α-1,6-fucosyltransferase gene, FUT8, knockout of CHO cells (see, for example, Yamane-Ohnuki et al.) Biotech. Bioeng. 87:614 (2004); Kanda et al. Biotechnol. Bioeng. 94(4):680-688 (2006); and WO2003 / 085107). Furthermore, antibody variants with bisected oligosaccharides are provided, for example, wherein the biantennary oligosaccharide attached to the Fc region of the antibody is bisected by GlcNAc. Such antibody variants may have reduced fucosylation and / or improved ADCC function. Examples of such antibody variants are described, for example, in WO 2003 / 011878 (Jean-Mairet et al.), US Patent No. 6,602,684 (Umana et al.); and US 2005 / 0123546 (Umana et al.). Antibody variants having at least one galactose residue in the oligosaccharide attached to the Fc region are also provided. Such antibody variants may have improved CDC function. Such antibody variants are described, for example, in WO 1997 / 30087 (Patel et al.); WO 1998 / 58964 (Raju, S); and WO 1999 / 22764 (Raju, S). c. Fc region variants In some specific embodiments, one or more amino acid modifications may be introduced into the Fc region of the antibody provided herein to generate Fc region variants. Fc region variants may include human Fc region sequences (e.g., human IgG1, IgG2, IgG3, or IgG4 Fc regions) that include amino acid modifications (e.g., substitutions) at one or more amino acid positions. In certain embodiments, the present invention envisions antibody variants possessing some, but not all, effector functions, making them ideal candidates for applications where the in vivo half-life of the antibody is important, but specific effector functions (such as complement and ADCC) are unnecessary or detrimental. In vitro and / or in vivo cytotoxicity assays can be performed to confirm a reduction / depletion of CDC and / or ADCC activity. For example, Fc receptor (FcR) binding assays can be performed to ensure that the antibody lacks FcγR binding (and therefore may lack ADCC activity), but retains FcRn binding capacity. The main cells regulating ADCC, NK cells, express only FcγRIII, while monocytes express FcγRI, FcγRII, and FcγRIII. FcR expression on hematopoietic cells is summarized in Ravetch and Kinet. Table 3 on page 464 of Annu. Rev. Immunol. 9:457-492 (1991). Non-limiting examples of in vitro assays for evaluating the ADCC activity of molecules 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); US Patent No. 5,821,337 (see Bruggemann et al.) J. Exp. Med. 166:1351-1361 (1987)). Alternatively, non-radioactive assays may be used (see, for example, the ACTI™ non-radioactive cytotoxicity assay for flow cytometry (Cell Technology, Inc. Mountain View, CA); and CytoTox 96). ® Non-radioactive cytotoxicity assays (Promega, Madison, WI). Useful effector cells for such assays include peripheral blood monocytes (PBMCs) and natural killer (NK) cells. Alternatively, or additionally, the ADCC activity of the molecules of interest can be assessed in vivo, for example in animal models, such as those used by Clynes et al. The assay is disclosed in Proc. Nat'l Acad. Sci. USA 95:652-656 (1998). A Clq binding assay can also be performed to determine if the antibody cannot bind Clq and therefore lacks CDC activity. See, for example, Clq and C3c binding ELISAs in WO 2006 / 029879 and WO 2005 / 100402. To assess complement activation, a CDC assay can be performed (see, for example, Gazzano-Santoro et al.). J. Immunol. Methods 202:163 (1996); Cragg et al. Blood101:1045-1052 (2003); and Cragg et al., Blood103:2738-2743 (2004)). FcRn binding and in vivo clearance / half-life determination can also be performed using methods known in the art (see, for example, Petkova et al.). Int'l. Immunol. 18(12):1759-1769 (2006)). Antibodies with reduced effector function include those with substitutions in one or more of the Fc region residues 238, 265, 269, 270, 297, 327, and 329 (US Patent No. 6,737,056). Such Fc mutants include Fc mutants with substitutions in two or more of the amino acid positions 265, 269, 270, 297, and 327, including the so-called “DANA” Fc mutant with residues 265 and 297 substituted with alanine (US Patent No. 7,332,581). Specific antibody variants that exhibit improved or weakened binding to FcR 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, the antibody variant includes an Fc region with one or more amino acid substitutions that enhance ADCC, such as substitutions at positions 298, 333, and / or 334 (EU numbers of residues) in the Fc region. In some embodiments, alterations are formed in the Fc region that result in altered (i.e., improved or reduced) Clq binding and / or complement-dependent cytotoxicity (CDC), for example, as described in U.S. Patent No. 6,194,551, WO 1999 / 51642, and by Idusogie et al. As described in J. Immunol.164:4178-4184 (2000). Antibodies that exhibit increased half-life and improved binding to the neonatal Fc receptor (FcRn) are described in US2005 / 0014934 (Hinton et al.), which is responsible for transferring maternal IgG to the fetus (Guyer et al.). J. Immunol. 117:587 (1976) and Kim et al. J. Immunol. 24:249 (1994). These antibodies include one or more Fc regions substituted therein, which improve the binding of the Fc region to FcRn. Such Fc variants contain one or more of the following Fc region residues: 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, ​​413, 424, or 434, with substitutions such as Fc region residue 434 (US Patent No. 7,371,826). For other examples of Fc region variants, please also refer to Duncan. Nature 322:738-40 (1988); US Patent No. 5,648,260; US Patent No. 5,624,821; and WO 1994 / 29351. d) Cysteine-modified antibody variants In certain embodiments, it is desirable to generate cysteine-modified antibodies, such as "thioMAb," in which one or more residues of the antibody are replaced by cysteine ​​residues. In particular embodiments, the substituted residues are located at easily accessible sites on the antibody. By replacing those residues with cysteine, a reactive thiol group is placed at an easily accessible site on the antibody and can be used to conjugate the antibody to other parts, such as a pharmaceutical part or to link a pharmaceutical part, to create immunoconjugates, as further described herein. In certain embodiments, any or more of the following residues may be replaced by cysteine: V205 (Kabat number) of the light chain; A118 (EU number) of the heavy chain; and S400 (EU number) of the Fc region of the heavy chain. Cysteine-modified antibodies can be generated, for example, as described in U.S. Patent No. 7,521,541. e) Antibody derivatives In some specific embodiments, the antibodies provided herein may be further modified to include additional non-protein moiety known in the art and readily available. Suitable moiety for antibody derivatization includes, but is not limited to, water-soluble polymers. Non-limiting examples of water-soluble polymers include, but are not limited to, polyethylene glycol (PEG), copolymers of ethylene glycol / propylene glycol, carboxymethyl cellulose, polydextrose, polyvinyl alcohol, polyvinylpyrrolidone, poly-1,3-dioxolane, and poly-1,3,6-triazine. Poly(1,3,6-trioxane), ethylene / maleic anhydride copolymers, polyamino acids (homomers or random copolymers), and polydextrose or poly(n-vinylpyrrolidone) polyethylene glycol, polypropylene glycol homopolymers, polypropylene oxide / ethylene oxide copolymers, polyoxyethylene alkylated polyols (e.g., glycerol), polyvinyl alcohol, and mixtures thereof. Polyethylene glycol propionaldehyde may have advantages in production due to its stability in water. Polymers may have any molecular weight and may be branched or unbranched. The number of polymers attached to the antibody may vary, and if more than one polymer is attached, they may be the same or different molecules. Generally, the number and / or type of polymers used for derivatization may be determined based on, including but not limited to, the specific properties or functions of the antibody to be improved, whether the antibody derivative will be used in a therapy under defined conditions, etc. In another embodiment, an antibody and a conjugate thereof that can be selectively heated by exposure to radiation are provided. In one embodiment, the non-protein portion is carbon nanotubes (Kam et al.). Proc. Natl. Acad. Sci. USA 102:11600-11605 (2005)). The radiation may have any wavelength, including but not limited to wavelengths that do not harm normal cells, but heat the non-protein portion to near the temperature at which the antibody-non-protein portion of the cell is killed. B. Recombinant methods and compositions. Antibodies can be generated using recombinant methods and compositions, such as those described in US 4,816,567. In one embodiment, an isolated nucleic acid encoding the anti-C5 antibody described herein is provided. Such nucleic acid may encode an amino acid sequence comprising VL and / or an amino acid sequence comprising VH of the antibody (e.g., the light and / or heavy chains of the antibody). In another embodiment, one or more vectors (e.g., expression vectors) comprising such nucleic acid are provided. In yet another embodiment, a host cell comprising such nucleic acid is provided. In this embodiment, the host cell comprises (e.g., having been transformed to have): (1) a vector comprising nucleic acid encoding an amino acid sequence comprising VL of the antibody and an amino acid sequence comprising VH of the antibody, or (2) a first vector comprising nucleic acid encoding an amino acid sequence comprising VL of the antibody, and a second vector comprising nucleic acid encoding an amino acid sequence comprising VH of the antibody. In one embodiment, the host cell is eukaryotic, such as Chinese hamster ovary (CHO) cells or lymphocytes (e.g., Y0, NSO, Sp20 cells). In one embodiment, a method for preparing an anti-C5 antibody is provided, wherein the method includes culturing a host cell, as provided above, comprising a nucleic acid encoding an antibody, under conditions suitable for antibody expression, and optionally recovering the antibody from the host cell (or host cell culture medium). For the recombinant production of anti-C5 antibodies, nucleic acids encoding the antibodies, as described above, are isolated and inserted into one or more vectors for further selection and / or expression in host cells. Such nucleic acids can be easily isolated and sequenced using standard procedures (e.g., by using oligonucleotide probes that can specifically bind to genes encoding the heavy and light chains of the antibody). Suitable host cells for the selection, colonization, or expression of vectors encoding antibodies include prokaryotic or eukaryotic cells as described herein. For example, antibodies can be produced in bacteria, particularly when glycosylation and Fc effector function are not required. For expression of antibody fragments and peptides in bacteria, see, for example, US 5,648,237, US 5,789,199, and US 5,840,523. (See also Charlton, Methods in Molecular Biology, Vol. 248 (edited by BKC Lo, Humana Press, Totowa, NJ, 2003), pp. 245-254, which describes the expression of antibody fragments in Escherichia coli. After expression, the antibody can be separated from the soluble fraction of bacterial cell paste and can be further purified. Besides prokaryotes, eukaryotic microorganisms such as filamentous fungi or yeasts are suitable hosts for the colonization or expression of antibody-encoding vectors. These include fungal and yeast strains whose glycosylation pathways have been "humanized," leading to the production of antibodies with partial or complete human glycosylation patterns. Please refer to Gerungross. Nat. Biotech. 22:1409-1414 (2004) and Li et al., Nat. Biotech. 24:210-215 (2006). Host cells suitable for the expression of glycosylated antibodies also originate from multicellular organisms (invertebrates and vertebrates). Examples of invertebrate cells include plant and insect cells. Several baculovirus strains have been identified that can be used in conjunction with insect cells, particularly for the transfection of fall armyworm (Spodoptera frugiperda) cells. Plant cell cultures can also be used as hosts. Please refer, for example, U.S. Patent Nos. 5,959,177, 6,040,498, 6,420,548, 7,125,978, and 6,417,429 (description of PLATNIBODIES™ technology for generating antibodies in genetically modified plants). Vertebrate cells can also be used as hosts. For example, mammalian cell lines adapted for growth in suspension can be used. Other examples of useful mammalian host cell lines are the monkey kidney CV1 cell line (COS-7) transformed with SV40; human embryonic kidney cell lines (293 or, for example, Graham et al., ... 293 cells as described in J. Gen Virol. 36:59 (1977); juvenile hamster kidney cells (BHK); mouse supporting cells (e.g., Mather, TM4 cells as described in Biol. Reprod. 23:243-251 (1980); monkey kidney cells (CV1); African green monkey kidney cells (VERO-76); human cervical cancer cells (HELA); canine kidney cells (MDCK); buffalo rat liver cells (BRL 3A); human lung cells (W138); human liver cells (Hep G2); mouse mammary tumors (MMT 060562); e.g., Mather et al. TRI cells, MRC 5 cells, and FS4 cells, as described in Annals NY Acad. Sci. 383:44-68 (1982). Other useful mammalian host cell lines include Chinese hamster ovary (CHO) cells, which contain DHFR -CHO cells (Urlaub et al., Proc. Natl. Acad. Sci. USA77:4216 (1980)); and myeloma cell lines, such as Y0, NS0, and Sp2 / 0. For reviews of specific mammalian host cell lines suitable for antibody production, please refer to, for example, Yazaki and Wu. Methods in Molecular Biology, Vol. 248 (edited by BKC Lo, Humana Press, Totowa, NJ), pp. 255-268 (2003). Polyclonal antibodies are preferably produced by repeated subcutaneous (sc) or intraperitoneal (ip) injections of the relevant antigen and adjuvant in animals. This can be achieved using bifunctional or derivatized reagents (e.g., maleimidobenzoyl sulfosuccinimide ester (conjugated via cysteine ​​residues), N-hydroxysuccinimide (conjugated via lysine residues), glutaraldehyde, succinic anhydride, SOCl₂). 2, or R 1 N═C═NR, where R and R 1 It is useful to couple relevant antigens to proteins (which are different alkyl groups) that are immunized against the species to be immunized (e.g., keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, or soybean trypsin inhibitors). Animals (typically non-human mammals) are immunized against an antigen, immunogenic conjugate, or derivative by intradermal injection of a solution, for example, 100 µg or 5 µg of protein or conjugate (for rabbits and mice, respectively), combined with three times the volume of Freund's complete adjuvant at multiple sites. One month later, animals are boosted with peptides or conjugates from 1 / 5 to 1 / 10 of the original amount of Freund's complete adjuvant by subcutaneous injection at multiple sites. Animals are bled between 7 and 14 days post-boost injection, and serum antibody titration concentrations are measured. Booster immunizations are continued until titer plateaus are reached. Preferably, booster immunizations are performed with conjugates of the same antigen, but conjugated to different proteins and / or using different cross-linking agents. Conjugates can also be generated in recombinant cell cultures as protein fusions. Aggregating agents such as alum are also suitable for enhancing immune responses. Monoclonal antibodies can be obtained from substantially homogeneous antibody populations, meaning that the individual antibodies in the population are identical, except for small amounts of naturally occurring mutations and / or post-translational modifications (e.g., isomerization, acetylation). Therefore, the modifier "monoclonal" indicates the characteristic of the antibody, which is not a mixture of dispersed antibodies. For example, monoclonal antibodies can be used by Kohler et al. The fusion tumor method was first described in Nature 256(5517): 495-497 (1975). In the fusion tumor method, mice or other suitable host animals, such as hamsters, are immunized as described herein to induce lymphocytes that produce or are able to produce antibodies that specifically bind to the immunization protein. Alternatively, the lymphocytes can be immunized in vitro. Immunoassay reagents typically contain proteins or fusion variants of antigens. Generally, peripheral blood lymphocytes (PBLs) are used if human-derived cells are required, or spleen cells or lymph node cells are used if non-human mammalian-derived cells are required. The lymphocytes are then fused with an immortalized cell line using a suitable fusion agent, such as polyethylene glycol, to form fusion tumor cells (Goding, Monoclonal Antibodies: Principles and Practice, Academic Press (1986), pp. 59-103). Immortalized cell lines are typically transformed mammalian cells, particularly rodent, bovine, and human myeloma cells. Rat or mouse myeloma cell lines are commonly used. The resulting fusion tumor cells are seeded and grown in a suitable culture medium, preferably containing one or more substances that inhibit the growth or survival of unfused, parental myeloma cells. For example, if the parental myeloma cells lack hypoxanthine-guanine phosphoribosyltransferase (HGPRT or HPRT), the fusion tumor culture medium will typically contain hypoxanthine, aminopterin, and thymine (HAT medium), which prevent the growth of HGPRT-deficient cells. Preferred immortalized myeloma cells are those that can efficiently fuse, support stable and high-quality antibody production via selected antibody-producing cells, and are sensitive to culture media (such as HAT medium). Among these, preferred are mouse myeloma lines, such as those derived from MOPC-21 and MPC-11 mouse tumors, available from the Salk Institute Cell Distribution Center, San Diego, California, USA, and SP-2 cells (and their derivatives, such as X-63-Ag8-653), available from the American Type Culture Collection, Manassas, Virginia, USA. Human myeloma and mouse-human hybrid myeloma cell lines have also been described for the production of human monoclonal antibodies (Kozbor et al., J Immunol. 133(6):3001-3005 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications; Marcel Dekker, Inc., New York (1987), pp. 51-63). The determination of whether monoclonal antibodies against the anti-antigen are produced in the culture medium for the growth of fusion tumor cells is preferred. The binding specificity of the monoclonal antibodies produced by the fusion tumor cells is preferably determined by immunoprecipitation or by in vitro binding assays (e.g., radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA)). Such techniques and assays are well known in the art. Binding affinity can be determined using Munson's method. The determination was performed using Scatchard analysis, as described in Anal Biochem. 107(1):220-239 (1980). After identifying fusion tumor cells with the desired specificity, affinity, and / or activity, these lines can be secondary colonized using standard methods (Goding, supra) through restricted dilution procedures and growth. Suitable culture media for this purpose include, for example, D-MEM or RPMI-1640 media. Furthermore, fusion tumor cells can grow in vivo as tumors in mammals. Monoclonal antibodies secreted by secondary colonies can be appropriately separated from culture medium, ascites fluid, or serum using conventional immunoglobulin purification procedures such as protein A-agarose, hydroxyphosphoric lime chromatography, colloidal electrophoresis, dialysis, or affinity chromatography. Antibodies can be generated by immunizing an appropriate host animal against an antigen. In one embodiment, the antigen is a polypeptide comprising the full-length C5. In one embodiment, the antigen is a polypeptide comprising the β chain of C5 (Sequence Identification Number: 40). In one embodiment, the antigen is a polypeptide comprising the MG1-MG2 domain of the β chain of C5 (Sequence Identification Number: 43). In one embodiment, the antigen is a polypeptide comprising the MG1 domain of the β chain of C5 (Sequence Identification Number: 41). In one embodiment, the antigen is a polypeptide comprising a region of amino acids corresponding to positions 19 to 180 of the β chain of C5. In one embodiment, the antigen is a polypeptide comprising a region of amino acids corresponding to positions 33 to 124 of the β chain of C5. In one embodiment, the antigen is a polypeptide comprising at least one fragment selected from amino acids 47-57, 70-76, and 107-110 of the β chain of C5 (Sequence Identification Number: 40). In one embodiment, the antigen is a polypeptide comprising a β-chain fragment of C5, comprising at least one amino acid selected from the group consisting of Thr47, Glu48, Ala49, Phe50, Asp51, Ala52, Thr53, Lys57, His70, Val71, His72, Ser74, Glu76, Val107, Ser108, ​​Lys109, and His110. In another embodiment, the antigen is a polypeptide comprising a β-chain fragment of C5, comprising at least one amino acid selected from the group consisting of Glu48, Asp51, His70, His72, Lys109, and His110. The present invention also includes antibodies produced by immunizing animals against the above-described antigens. Antibodies may combine any of these features individually or in combination, as described in the "Exemplary Anti-C5 Antibody" section above. C. Assay The physical / chemical properties and / or biological activity of the anti-C5 antibody presented herein can be identified, screened, or characterized using a variety of assays known in the art. 1. Binding assays and other assays In a single state, for example, through familiar methods such as ELISA, Western ink application, and BIACORE. ® The antibodies of this invention were tested for their antigen-binding activity. In another embodiment, a competitive assay can be used to identify antibodies that compete with the anti-C5 antibodies described herein for binding to C5. In some specific embodiments, when such competitive antibodies are present in excess, they inhibit (e.g., reduce) the binding of the reference antibody to C5 by at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, or more. In some examples, binding is inhibited by at least 80%, 85%, 90%, 95%, or more. In some specific embodiments, such competitive antibodies bind to the same antigenic determinant (e.g., linear or conformational antigenic determinant) as the anti-C5 antibody described herein (e.g., the antibody described in Table 2). Detailed exemplary methods for locating antigenic determinants for antibody binding are described in Morris, “Epitope Mapping Protocols,” in Methods in Molecular Biology vol. 66 (Humana Press, Totowa, NJ) (1996) are available. In an exemplary competitive assay, immobilized C5 is cultured in a solution comprising a first labeled (reference) antibody bound to C5 and a second unlabeled antibody tested for its ability to compete with the first antibody for binding to C5. The second antibody may be present in the supernatant of the fusion tumor. As a control, immobilized C5 is cultured in a solution comprising the first labeled antibody but excluding the second labeled antibody. After culturing under conditions allowing the first antibody to bind to C5, excess unbound antibody is removed, and the amount of labeled antibody bound to the immobilized C5 is measured. If the amount of labeled antibody bound to the immobilized C5 in the test sample is substantially reduced relative to the control sample, it indicates that the second antibody is competing with the first antibody for binding to C5. See Harlow and Lane. Antibodies: A Laboratory Manualch.14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY) (1988). In another exemplary competitive assay, BIACORE was used. ®The analysis uses a second (reference) anti-C5 antibody to determine the competitive binding ability of the tested anti-C5 antibody to C5. In another sample, following manufacturer recommendations, a BIACORE® instrument (e.g., BIACORE® 3000) is operated to capture the C5 protein onto a CM5 BIACORE® wafer using established standard techniques to create a C5-coated surface. Typically, 200 to 800 resonance units of C5 are attached to the wafer (this amount provides a simple, measurable level of binding but can easily be saturated by the concentration of the test antibody used). The two antibodies (i.e., test and reference antibodies) to be evaluated for their competitive ability are mixed in a suitable buffer at a 1:1 molar ratio of binding sites to produce a test mixture. When calculating concentrations based on binding sites, the molecular weight of the test or reference antibody is assumed to be the total molecular weight of the corresponding antibody divided by the number of C5 binding sites on that antibody. The concentration of each antibody (i.e., test and reference antibody) in the test mixture should be high enough to facilitate capture onto the BIACORE. ® The binding sites of the antibody on the C5 molecule on the wafer are saturated. The antibodies in the mixture have the same molar concentration (on a binding basis), typically between 1.00 and 1.5 μmol (on a binding site basis). Separate solutions containing individual test antibodies and individual reference antibodies are also prepared. The test antibodies and reference antibodies in these solutions should be in the same buffer and at the same concentrations and conditions as the test mixture. The test mixture containing the test antibody and reference antibody is passed through a C5-coated BIACORE. ® The total amount bound is recorded on the wafer. The wafer is then treated to remove the bound test or reference antibody without destroying the C5 coating on the wafer. Typically, this is done by treating the wafer with 30 mM HCl for 60 seconds. A solution of the individual test antibody is then passed through the C5-coated surface, and the amount bound is recorded. The wafer is treated again to remove all bound antibodies without destroying the C5 coating on the wafer. A solution of the individual reference antibody is then passed through the C5-coated surface, and the amount bound is recorded. The maximum theoretical binding of the mixture of test and reference antibodies is then calculated, which is the sum of the bindings of each antibody (test and reference) when only the C5 surface is passed. If the actual recorded binding of the mixture is less than this theoretical maximum, then the test and reference antibodies compete with each other for binding to the C5. Therefore, generally, competitive testing of anti-C5 antibodies occurs in the above-mentioned BIACORE. ®The blocking assay binds to C5 such that, during the assay and in the presence of a reference anti-C5 antibody, the recorded binding is between 80% and 0.1% of the maximum theoretical binding (e.g., 80% to 4%), specifically between 75% and 0.1% of the maximum theoretical binding (e.g., 75% to 4%), and more specifically between 70% and 0.1% of the maximum theoretical binding (as defined above) of the combined test and reference antibody (e.g., 70% to 4%). In some specific embodiments, the anti-C5 antibody of the present invention competitively binds to C5 with antibodies including VH and VL pairs selected from antibodies CFA0341 and CFA0330. In some embodiments, the anti-C5 antibody competitively binds to C5 with antibodies selected from: CFA0538, CFA0501, CFA0599, CFA0307, ​​CFA0366, CFA0675, and CFA0672. In some embodiments, the anti-C5 antibody competitively binds to C5 with antibody CFA0329. In some embodiments, the anti-C5 antibody competitively binds to C5 with antibody CFA0666. In some specific embodiments, the anti-C5 antibody of the present invention competitively binds to C5 with antibodies comprising VH and VL pairs including antibody CFA0305 or 305LO5. In some other embodiments, the anti-C5 antibody binds to C5 with higher affinity at neutral pH compared to acidic pH. In some specific embodiments, the anti-C5 antibody of the present invention competitively binds to C5 with antibodies comprising VH and VL pairs selected from: CFA0538, CFA0501, CFA0599, CFA0307, ​​CFA0366, CFA0675, and CFA0672. In some embodiments, the anti-C5 antibody competitively binds to C5 with antibody CFA0666. In still other embodiments, the anti-C5 antibody binds to C5 with higher affinity at pH 7.4 compared to pH 5.8. In some other embodiments, the anti-C5 antibody binds to C5 with higher affinity at neutral pH compared to acidic pH. In some specific embodiments, the anti-C5 antibody of the present invention competitively binds to C5 with antibodies comprising VH and VL pairs including antibody CFA0305 or 305LO5. In still other embodiments, the anti-C5 antibody binds to C5 with higher affinity at pH 7.4 compared to pH 5.8. In some specific embodiments, the anti-C5 antibody of the present invention competitively binds to C5 with antibodies against VH and VL selected from sequence identification number 22 and sequence identification number 26, or VH selected from sequence identification number 21 and VL selected from sequence identification number 25. In some embodiments, the anti-C5 antibody comprises the VH selected from: (a) sequence identifier: 5 and VL select: 15; (b) sequence identifier: 4 and VL select: 14; (c) sequence identifier: 6 and VL select: 16; (d) sequence identifier: 2 and VL select: 12; (e) sequence identifier: 3 and VL select: 13; (f) sequence identifier: 1 and VL select: 11; (g) sequence identifier: 9 and VL select: 19; (h) sequence identifier: 7 and VL select: 17; and (i) Antibodies against the VH and VL of sequence identifier 8 and sequence identifier 18 compete for binding to C5. In some embodiments, the anti-C5 antibody competes for binding to C5 with antibodies including the VH of sequence identifier 23 and the VL of sequence identifier 27. In some embodiments, the anti-C5 antibody competes for binding to C5 with antibodies including the VH of sequence identifier 7 and the VL of sequence identifier 17. In some specific embodiments, the anti-C5 antibody of the present invention comprises the following: (a) VH of sequence identifier: 1 and VL of sequence identifier: 11; (b) VH of sequence identifier: 22 and VL of sequence identifier: 26; (c) VH of sequence identifier: 21 and VL of sequence identifier: 25; (d) VH of sequence identifier: 5 and VL of sequence identifier: 15; (e) VH of sequence identifier: 4 and VL of sequence identifier: 14; (f) VH of sequence identifier: 6 and VL of sequence identifier: 16; (g) VH of sequence identifier: 2 and VL of sequence identifier: 12; (h) VH of sequence identifier: 3 and VL of sequence identifier: 13; (i) VH of sequence identifier: 9 and VL of sequence identifier: 19; (j) (k) VH of sequence identifier: 7 and VL of sequence identifier: 17; (l) VH of sequence identifier: 8 and VL of sequence identifier: 18; and (m) VH and VL of sequence identifier: 23 and VL of sequence identifier: 27, competitively binding to C5 by the antibody against VH and VL of VH and VL of sequence identifier: 10 and VL of sequence identifier: 20. In some specific embodiments, the anti-C5 antibody of the present invention comprises the following: (a) VH of sequence identifier 22 and VL of sequence identifier 26; (b) VH of sequence identifier 21 and VL of sequence identifier 25; (c) VH of sequence identifier 5 and VL of sequence identifier 15; (d) VH of sequence identifier 4 and VL of sequence identifier 14; (e) VH of sequence identifier 6 and VL of sequence identifier 16; (f) VH of sequence identifier 2 and VL of sequence identifier 12; (g) VH of sequence identifier 3 and VL of sequence identifier 13; (h) VH of sequence identifier 9 and VL of sequence identifier 19; (i) VH of sequence identifier 7 and VL of sequence identifier 17; (j) VH with sequence identifier: 8 and VL with sequence identifier: 18; (k) VH with sequence identifier: 23 and VL with sequence identifier: 27 competitively bind to C5 against the antibody. In some specific embodiments, the anti-C5 antibody of the present invention competitively binds to C5 with antibodies against VH and VL selected from sequence identification number 1 and sequence identification number 11, or VH selected from sequence identification number 10 and VL selected from sequence identification number 20. In some other embodiments, the anti-C5 antibody binds to C5 with higher affinity at neutral pH compared to acidic pH. In some specific embodiments, the anti-C5 antibody binds to C5 with higher affinity at neutral pH than at acidic pH, and with a subset of: (a) VH of sequence identifier: 1 and VL of sequence identifier: 11; (b) VH of sequence identifier: 5 and VL of sequence identifier: 15; (c) VH of sequence identifier: 4 and VL of sequence identifier: 14; (d) VH of sequence identifier: 6 and VL of sequence identifier: 16; (e) VH of sequence identifier: 2 and VL of sequence identifier: 12; (f) VH of sequence identifier: 3 and VL of sequence identifier: 13; (g) VH of sequence identifier: 9 and VL of sequence identifier: 19; (h) VH of sequence identifier: 7 and VL of sequence identifier: 17; (i) The VH and VL of sequence identifier 8 and sequence identifier 18; and (j) the VH and VL of sequence identifier 10 and sequence identifier 20, respectively, competitively bind to C5 against their respective antibodies. In some other embodiments, the anti-C5 antibody binds to C5 with higher affinity at pH 7.4 compared to at pH 5.8. In some embodiments, the anti-C5 antibody binds to C5 with higher affinity at neutral pH than at acidic pH, and includes the following: (a) VH of sequence identifier: 5 and VL of sequence identifier: 15; (b) VH of sequence identifier: 4 and VL of sequence identifier: 14; (c) VH of sequence identifier: 6 and VL of sequence identifier: 16; (d) VH of sequence identifier: 2 and VL of sequence identifier: 12; (e) VH of sequence identifier: 3 and VL of sequence identifier: 13; (f) VH of sequence identifier: 1 and VL of sequence identifier: 11; (g) VH of sequence identifier: 9 and VL of sequence identifier: 19; (h) VH of sequence identifier: 7 and VL of sequence identifier: 17; and (i) The VH and VL of sequence identifier 8 and sequence identifier 18 competitively bind to C5. In some other embodiments, the anti-C5 antibody binds to C5 with higher affinity at pH 7.4 compared to at pH 5.8. In some embodiments, the anti-C5 antibody binds to C5 with higher affinity at neutral pH than at acidic pH, and competes with antibodies against VH and VL pairs selected from: VH of sequence identifier 1 and VL of sequence identifier 11, or VH of sequence identifier 10 and VL of sequence identifier 20. In still other embodiments, the anti-C5 antibody binds to C5 with higher affinity at pH 7.4 than at pH 5.8. In some specific embodiments, whether the anti-C5 antibody of the present invention binds to a specific antigenic determinant can be determined as follows: A C5 point mutant expressing alanine-substituted amino acids (except alanine) on C5 is expressed in 293 cells, and this is determined by ELISA, Western Spectroscopy, or BIACORE assay. ® The binding of the anti-C5 antibody to the C5 mutant is tested; where a substantially reduced or absent binding of the anti-C5 antibody to the C5 mutant compared to its binding to wild-type C5 represents binding of the anti-C5 antibody to the antigenic determinant including that amino acid on C5. In some specific embodiments, the amino acid to be substituted for alanine on C5 is selected from the group consisting of Glu48, Asp51, His70, His72, Lys109, and His110 of the β chain of C5 (Sequence Identification Number: 40). In still other embodiments, the amino acid to be substituted for alanine on C5 is either Asp51 or Lys109 of the β chain of C5 (Sequence Identification Number: 40). In another embodiment, whether an anti-C5 antibody with pH-dependent binding properties binds to a specific antigenic determinant can be determined as follows: A C5 point mutant in 293 cells, in which the histidine residue on C5 is replaced by another amino acid (e.g., tyrosine), is expressed, and the binding is determined by ELISA, Western Spot Analyzer, or BIACORE. ® The binding of the anti-C5 antibody to the C5 mutant was tested; where a substantially reduced binding of the anti-C5 antibody to wild-type C5 at acidic pH compared to its binding to the C5 mutant at acidic pH represents binding of the anti-C5 antibody to the antigenic determinant including that histidine residue on C5. In some other embodiments, the binding of the anti-C5 antibody to wild-type C5 at neutral pH was not substantially reduced compared to its binding to the C5 mutant at neutral pH. In some specific embodiments, the histidine residue on C5 to be replaced by another amino acid is selected from the group consisting of His70, His72, and His110 of the β chain of C5 (Sequence Identification Number: 40). In yet another embodiment, the histidine residue His70 is replaced by tyrosine. 2. Activity Assay In one embodiment, assays are provided to identify the biological activities of the anti-C5 antibody. These biological activities may include, for example, inhibiting C5 activation, preventing C5 cleavage to form C5a and C5b, hindering C5 convertase access to the cleavage site on C5, and inhibiting hemolytic activity resulting from C5 activation. Antibodies exhibiting these biological activities in vivo and / or in vitro are also provided. In some specific embodiments, the biological activities of the antibodies of the present invention are tested. In some specific embodiments, testing whether the antibody inhibits the cleavage of C5 into C5a and C5b is performed by, for example, Isenman et al. The method described in J Immunol. 124(1):326-331 (1980) is used for determination. In another embodiment, this is performed by a method that specifically detects cleaved C5a and / or C5b proteins, such as ELISA or Western spotting. The test antibody is considered to be an antibody that inhibits C5 cleavage if a reduced amount of C5 cleavage products (C5a and / or C5b) is detected in the presence of the test antibody (or after contact with the test antibody). In some specific embodiments, the concentration and / or physiological activity of C5a can be measured by, for example, chemotactic assays, RIA, or ELISA (see, for example, Ward and Zvaifler). J. Clin. Invest. 50(3):606-616 (1971)). In some specific embodiments, the test for whether the antibody prevents C5 convertase from approaching C5 is determined by methods used to detect protein interactions between C5 convertase and C5, such as ELISA or BIACORE. ® The test antibody is considered to be an antibody that can prevent C5 convertase from approaching C5 when the interaction is reduced in the presence of the test antibody (or after contact with the test antibody). In some specific embodiments, C5 activity can be measured as a function of its ability to lyse cells in the body fluids of a subject. This can be achieved using methods known in the art, such as conventional hemolysis assays, like those described in Kabat and Mayer (eds.), Experimental Immunochemistry, 2nd Edition, 135-240, Springfield, IL, CC Thomas (1961), pages 135-139, or conventional variations of such assays, such as those described by Hillmen et al. (2004). The method for measuring the cytolytic capacity of C5 or its decrease, as described in N. Engl. J. Med. 350(6): 552-559 (2004), is used to describe chicken erythrocyte hemolysis. In some specific embodiments, the CH50eq assay is used to quantify C5 activity or its inhibition. The CH50eq assay is a method for measuring total classical complement activity in serum. This assay is a lytic assay that uses antibody-sensitized erythrocytes as activators of the classical complement pathway and uses multiple dilutions of the test serum to determine the amount required to achieve 50% cell lysis (CH50). The percentage of hemolysis can be determined, for example, using a spectrophotometer. The CH50eq assay provides an indirect measurement of terminal complement complex (TCC) formation, as the TCC itself is directly responsible for the hemolysis measured. Inhibition of C5 activation can also be detected and / or measured using the methods exemplified and illustrated in the operational embodiments. Using these or other types of assays, candidate antibodies capable of inhibiting C5 activation can be screened. In some specific embodiments, compared to the effect of the negative control group under similar conditions, inhibition of C5 activation includes a reduction of at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% or more of C5 activity in the assay. In some embodiments, it represents inhibition of at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% or more of C5 activation. D. Immunoconjugates The present invention also provides immunoconjugates comprising the anti-C5 antibody described herein conjugated to one or more cytotoxic agents, such as chemotherapeutic agents or drugs, growth inhibitors, toxins (e.g., bacterial, fungal, plant or animal-derived protein toxins, enzyme-active toxins, or fragments thereof) or radioisotopes. In one embodiment, the immunoconjugate is an antibody-drug conjugate (ADC), wherein the antibody is conjugated to one or more drugs, including but not limited to maytansinoid (see U.S. Patent Nos. 5,208,020, 5,416,064 and European Patent EP 0 425 235 B1); auristatin, such as the monomethyl auristatin drug moieties DE and DF (MMAE and MMAF) (see U.S. Patent Nos. 5,635,483, 5,780,588 and 7,498,298); dolastatin; calicheamicin or derivatives thereof (see U.S. Patent Nos. 5,712,374, 5,714,586, 5,739,116, 5,767,285, 5,770,701, 5,770,710). 5,773,001 and 5,877,296; Hinman et al. Cancer Res. 53:3336-3342 (1993); and Lode et al., Cancer Res. 58:2925-2928 (1998)); anthracycline antibiotics such as daunomycin or doxorubicin (see Kratz et al., Current Med. Chem. 13:477-523 (2006); Jeffrey et al. Bioorganic & Med. Chem. Letters16:358-362 (2006); Torgov et al., Bioconj. Chem. 16:717-721 (2005); Nagy et al. Proc. Natl. Acad. Sci. USA 97:829-834 (2000); Dubowchik et al. Bioorg. & Med. Chem. Letters12:1529-1532 (2002); King et al., J. Med. Chem. 45:4336-4343 (2002); and US Patent No. 6,630,579); methotrexate; vindesine; taxanes such as docetaxel, paclitaxel, irataxel, tesetaxel, and ortataxe; trichothecene; and CC1065. In another embodiment, the immunoconjugate comprises an antibody conjugated to an enzymatically active toxin or a fragment thereof as described herein, including, but not limited to, diphtheria A chain, a non-binding active fragment of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain, sarcin, Aleutites fordii, dianthin, Phytolacca americana protein (PAPI, PAPII, and PAP-S), Momordica charantia inhibitor, curcin, crotin, and sapaonaria. Inhibitors of citric acid, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and trichothecene. In another embodiment, the immunoconjugate comprises an antibody, as described herein, coupled to a radioactive atom to form a radioconjugate. A variety of radioisotopes can be used to manufacture radioconjugates. Examples include At. 211 , I 131 , I 125 Y 90 Re 186 Re 188 , Sm 153 Bi 212 , P 32 Pb 212 And radioactive isotopes of Lu. When using radiocouples for detection, it may include radioactive atoms for scintillation studies, such as tc-99m or I123, or spin labels for nuclear magnetic resonance (NMR) imaging (also known as magnetic resonance imaging, MRI), such as iodine-123, iodine-131, indium-111, fluorine-19, carbon-13, nitrogen-15, oxygen-17, thiocyanate, manganese, or iron. A variety of bifunctional protein conjugates can be used to form conjugates of antibodies and cytotoxic agents, such as N-succinimino-3-(2-pyridyl dithio)propionate (SPDP), succinimino-4-(N-maleiminomethyl)cyclohexane-I-carboxylate (SMCC), iminothiones (IT), bifunctional derivatives of imine esters (e.g., hexamethylenediimino hydrochloride), active esters (e.g., disuccinimino octanoate), aldehydes (e.g., glutaraldehyde), diazid compounds (e.g., bis(p-azidobenzoyl)hexamethylenediamine), diazide derivatives (e.g., bis(p-diazobenzoyl)-ethylenediamine), diisocyanates (e.g., toluene 2,6-diisocyanate), and bifunctional fluorinated compounds (e.g., 1,5-difluoro-2,4-dinitrobenzene). For example, as Vitetta et al., The preparation of ricin immunotoxin is described in Science 238:1098 (1987). Carbon-14 labeled benzyl-3-methyldiethylenetriaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugating radioactive nucleotides to antibodies. See WO94 / 11026. The linker can be a “cleavable linker” that facilitates the release of cytotoxic drugs into cells. For example, acid-labile linkers, peptidase-sensitive linkers, light-labile linkers, dimethyl linkers, or disulfide-containing linkers can be used (Chari et al., ...). Cancer Res. 52:127-131 (1992); US Patent No. 5,208,020. The immunoconjugates or ADCs described herein are explicitly envisioned, but not limited to, such conjugates prepared using cross-linking agents, including but not limited to BMPS, EMCS, GMBS, HBVS, LC-SMCC, MBS, MPBH, SBAP, SIA, SIAB, SMCC, SMPB, SMPH, sulfo-EMCS, sulfo-GMBS, sulfo-KMUS, sulfo-MBS, sulfo-SIAB, sulfo-SMCC, and sulfo-SMPB, and SVSB (succinimino-(4-vinyl benzoate)benzoate), which are commercially available (e.g., from Pierce Biotechnology, Inc., Rockford, IL., USA). E. Methods and compositions for diagnosis and detection. In some specific embodiments, any of the anti-C5 antibodies provided herein are useful for detecting the presence of C5 in biological samples. The term "detect," as used herein, encompasses both quantitative and qualitative detection. In some specific embodiments, biological samples include cells or tissues such as serum, whole blood, plasma, tissue sections, tissue samples, cell suspensions, saliva, sputum, oral fluid, cerebrospinal fluid, amniotic fluid, ascites, milk, colostrum, mammary gland secretions, lymph, urine, sweat, tears, gastric juice, synovial fluid, peritoneal fluid, intraocular fluid, and mucus. In one embodiment, an anti-C5 antibody is provided for use in a diagnostic or detection method. In another embodiment, a method for detecting the presence of C5 in a biological sample is provided. In some specific embodiments, this method includes contacting a biological sample with an anti-C5 antibody as described herein, under conditions that allow the anti-C5 antibody to bind to C5, and detecting whether a complex is formed between the anti-C5 antibody and C5. This method may be in vitro or in vivo. In one embodiment, the anti-C5 antibody is used to select suitable subjects for anti-C5 antibody therapy, for example, where C5 is a biomarker for patient selection. In another embodiment, a method is provided for selecting an individual with a complement regulation disease or condition involving excessive or uncontrolled C5 activation as a suitable therapy comprising the anti-C5 antibody of the present invention. In some specific embodiments, the method comprises (a) detecting a genetic variation in C5 originating from the individual, and (b) when a genetic variation in C5 originating from the individual is detected, selecting the individual as a suitable therapy comprising the anti-C5 antibody of the present invention. In another embodiment, a method is provided for selecting a therapy for an individual with a complement regulation disease or condition involving excessive or uncontrolled C5 activation. In some specific embodiments, the method comprises (a) detecting a genetic variation in C5 originating from the individual, and (b) when a genetic variation in C5 originating from the individual is detected, selecting a therapy comprising the anti-C5 antibody of the present invention for the individual. In another embodiment, a method is provided for treating an individual with a complement regulation disease or condition involving excessive or uncontrolled C5 activation. In some specific embodiments, the method includes (a) detecting a genetic variation in C5 originating from the individual, (b) when a genetic variation in C5 originating from the individual is detected, selecting an individual as a suitable candidate for a therapy comprising the anti-C5 antibody of the present invention, and (c) administering the anti-C5 antibody of the present invention to the individual. In another embodiment, the use of the anti-C5 antibody of the present invention is provided for treating individuals with complement regulation disorders or conditions involving excessive or uncontrolled C5 activation. In some specific embodiments, the individual is treated with the anti-C5 antibody of the present invention when a genetic variation in C5 originating from the individual is detected. In another embodiment, in vivo use of genetic variations of C5 is provided for selecting individuals with complement regulation diseases or conditions involving excessive or uncontrolled C5 activation as suitable recipients of a therapy comprising the anti-C5 antibody of the present invention. In some specific embodiments, when a genetic variation of C5 originating from an individual is detected, an individual suitable for the therapy is selected. In another embodiment, in vivo use of genetic variations of C5 is provided for selecting a therapy for individuals with complement regulation diseases or conditions involving excessive or uncontrolled C5 activation. In some specific embodiments, when a genetic variation of C5 originating from an individual is detected, a therapy comprising the anti-C5 antibody of the present invention is selected for the individual. There have been reports of some patients with genetic variants in C5 showing adverse responses to therapies containing pre-existing anti-C5 antibodies (Nishimura et al., N). Engl. J. Med. 370:632-639 (2014)). Such patients are recommended to be treated with a therapy containing the anti-C5 antibody of this origin, as this antibody has inhibitory activity against activation of both C5 variants and wild-type C5, as shown in the following examples. Detection of genetic variations in C5 can be performed using methods known in the art. Such methods may include, but are not limited to, sequencing, PCR, RT-PCR, and hybridization-based methods, such as southern or northern speckle analysis. C5 variants may contain at least one genetic variation. The genetic variation may be selected from the group consisting of V145I, R449G, V802I, R885H, R928Q, D966Y, S1310N, and E1437D. Herein, R885H, for example, represents a genetic variation in which arginine at position 885 is replaced by histidine. In some specific embodiments, C5 variants exhibit biological activity similar to wild-type C5. Exemplary diseases that can be diagnosed using the antibodies of this invention include rheumatoid arthritis (RA); systemic lupus erythematosus (SLE); lupus nephritis; ischemia-reperfusion injury (IRI); asthma; paroxysmal nocturnal hemoglobinuria (PNH); hemolytic uremic syndrome (HUS) (e.g., atypical hemolytic uremic syndrome (aHUS)); dense deposit disease (DDD); neuromyelitis optica (NMO); multifocal motor neuropathy (MMN); and multiple sclerosis. MS; Systemic sclerosis; Macular degeneration (e.g., age-related macular degeneration (AMD)); Hemolysis, elevated liver enzymes, and HELLP syndrome; Thrombotic thrombocytopenic purpura (TPP); Spontaneous fetal loss; Epidermolysis bullosa; Recurrent fetal loss; Preeclampsia; Traumatic brain injury; Myasthenia gravis; Cold agglutinin syndrome; Sjögren's syndrome; Dermatomyositis; Bullous pemphigoid; Phototoxic reaction; Shiga toxin-associated hemolytic uremic syndrome. E. coli-related hemolytic uremic syndrome; typical or infectious hemolytic uremic syndrome (tHUS); C3 glomerulonephritis; anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis; humoral and vascular transplant rejection; acute antibody-mediated rejection (AMR); graft dysfunction; myocardial infarction; allogeneic transplantation; sepsis; coronary artery disease; hereditary angioedema; dermatomyositis; Graves' disease; atherosclerosis; Alzheimer's disease (AD); Huntington's disease; Creutzfeld-Jacob's disease; Parkinson's disease. Disease; Cancer; Wound; Septic shock; Spinal cord injury; Uveitis; Diabetic retinopathy; Retinopathy of prematurity; Glomerulonephritis; Membranous nephritis; Immunoglobulin A nephropathy; Adult respiratory distress syndrome (ARDS); Chronic obstructive pulmonary disease (COPD); Cystic fibrosis; Hemolytic anemia; Paroxysmal cold hemoglobinuria; Anaphylactic shock; Allergy; Osteoporosis; Osteoarthritis; Hashimoto's thyroiditis; Type I diabetes; Psoriasis; Pemphigus; Autoimmune hemolytic anemia AIHA; idiopathic thrombocytopenic purpura (ITP); Goodpasture syndrome; Degos disease; antiphospholipid syndrome (APS);Catastrophic antiphospholipid syndrome (CAPS); cardiovascular disease; myocarditis; cerebrovascular disorder; peripheral vascular disease; renal vascular disease; mesenteric / enteric vascular disorder; vasculitis; Henoch-Schönlein purpura nephritis; Takayasu's disease; dilated cardiomyopathy; diabetic angiopathy; Kawasaki's disease (arteritis); venous gas embolus (VGE); restenosis following stent placement; rotational atherectomy; membranous nephropathy; Guillain-Barré syndrome (GBS); Fisher syndrome. Syndrome; antigen-induced arthritis; synovitis; viral infection; bacterial infection; fungal infection; and damage caused by myocardial infarction, cardiopulmonary bypass, and hemodialysis. In some specific embodiments, labeled anti-C5 antibodies are provided. Labeling includes, but is not limited to, labels or portions that are directly detected (e.g., fluorescence, chromophores, electron-dense, chemiluminescent, and radioactive labels), and portions that are detected indirectly (e.g., via enzymatic reactions or molecular interactions), such as enzymes or ligands. Exemplary labels include, but are not limited to, radioisotopes. 32 P, 14 C 125 I, 3 H and 131I. Luminescent groups such as rare earth chelates or luciferin and its derivatives, rhodamine and its derivatives, dansyl, umbellifeixme, luciferase, for example, firefly luciferase and bacterial luciferase (US Patent No. 4,737,456), luciferin, 2,3-dihydrophthalazinedione, horseradish peroxidase (HRP), alkaline phosphatase, β-galactosidase, glucosylamylase, dissolving enzymes, carbohydrate oxidases, such as glucose oxidase, galactose oxidase and glucose-6-phosphate dehydrogenase, heterocyclic oxidases such as uricase and xanthine oxidase, enzymes that utilize hydrogen peroxide to oxidize dye precursors such as HRP, lactoperoxidase, or microperoxidase, biotin / avidin, spin-labeled substances, phage labels, stable free radicals, etc. F. Pharmaceutical formulations The pharmaceutical formulation of the anti-C5 antibody described herein involves combining this antibody, which has the desired level of purity, with one or more optional pharmaceutically acceptable carriers. Remington's Pharmaceutical Sciences, 16th edition, Osol, A. Ed. (1980)) , prepared as a lyophilized formulation or an aqueous solution. Pharmaceutically acceptable carriers are generally non-toxic to recipients at the doses and concentrations used and include, but are not limited to: buffers such as phosphates, citrates and other organic acids; antioxidants, including ascorbic acid and methionine; preservatives (such as octadecyl dimethyl benzyl ammonium chloride; hexahydroxy quaternary ammonium chloride; benzalkonium chloride; benzyl chloride; phenol; butanol or benzyl alcohol; alkyl parabens such as methylparaben or propylparaben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 (1 residue) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers, such as polyvinylpyrrolidone; amino acids, such as glycine, glutamine, aspartic acid, histidine, arginine, or lysine; monosaccharides, disaccharides, and other sugars, including glucose, mannose, or dextrin; chelating agents, such as EDTA; sugars, such as sucrose, mannitol, trehalose, or sorbitol; salt-forming ions, such as sodium; metal complexes (e.g., Zn-protein complexes); and / or nonionic surfactants, such as polyethylene glycol (PEG). Exemplary pharmaceutically acceptable carriers described herein also include interstitial drug dispersants, such as soluble neutral-active hyaluronidase glycoprotein (sHASEGP), for example, human soluble PH-20 hyaluronidase glycoprotein, such as rHuPH20 (HYLENEX). ®(Baxter International, Inc.). Specific exemplary sHASEGP and methods of use, including rHuPH20, are described in U.S. Patent Publications 2005 / 0260186 and 2006 / 0104968. In one embodiment, sHASEGP is combined with one or more additional glucosamine enzymes, such as chondroitinase. Exemplary lyophilized antibody formulations are described in U.S. Patent No. 6,267,958. Aqueous antibody formulations include those described in U.S. Patent Nos. 6,171,586 and WO 2006 / 044908, the latter of which contains histidine-acetate buffer. The formulation described herein may also contain more than one active ingredient, preferably those that do not adversely affect each other's complementary activities if required for the specific indication being treated. These active ingredients are appropriately combined in amounts effective for the intended use. Active ingredients can be retained in microcapsules, for example, those prepared by coagulation techniques or interfacial polymerization, such as hydroxymethyl cellulose or gelatin microcapsules and poly-(methyl methacrylate) microcapsules, respectively, in colloidal drug delivery systems (e.g., liposomes, albumin microspheres, microemulsions, nanoparticles, and nanocapsules) or in coarse droplet emulsions. Such techniques are disclosed in… Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980). Sustained-release formulations can be prepared. Suitable examples of sustained-release formulations include a semi-permeable matrix of a solid hydrophobic polymer containing an antibody, said matrix being in the form of a shaped article, such as a film or microcapsule. Formulations intended for internal administration are typically sterile. Sterility can be easily achieved, for example, through filtration via a sterile filter membrane. G. Treatment methods and compositions Any of the anti-C5 antibodies provided in this article can be used for treatment. In one embodiment, an anti-C5 antibody is provided for use as a medicament. In yet another embodiment, an anti-C5 antibody is provided for treating complement regulation diseases or conditions involving excessive or uncontrolled C5 activation. In some specific embodiments, an anti-C5 antibody is provided for use in a treatment method. In some specific embodiments, the present invention provides an anti-C5 antibody for treating an individual with a complement regulation disease or condition involving excessive or uncontrolled C5 activation, the method comprising administering an effective amount of the anti-C5 antibody to the individual. In such an embodiment, the method further comprises administering an effective amount of at least one additional therapeutic agent to the individual. The "individual" according to any of the above embodiments is preferably a human being. When antibodies are soluble proteins, their binding to antigens can prolong the half-life of the antigen in plasma (i.e., reduce the elimination of the antigen from the plasma), because antibodies themselves have a long half-life in plasma and act as carriers of antigens. This is due to the recovery of the antigen-antibody complex via the endosome pathway in cells through FcRn (Roopenian pathway). Nat. Rev. Immunol. 7(9):715-725 (2007)). However, antibodies with pH-dependent binding properties, which bind to their antigens in a neutral extracellular environment and then release them into the acidic intracellular compartment after entering the cell, are expected to have superior properties in antigen neutralization and clearance compared to their counterparts that bind in a non-pH-dependent manner (Igawa et al., Nat. Biotech..28(11):1203-1207 (2010); Devanaboyina et al., mAbs5(6):851-859 (2013); WO 2009 / 125825). In some other embodiments, the invention provides a primary anti-C5 antibody for enhancing the elimination of C5 from plasma. In some specific embodiments, the invention provides a primary anti-C5 antibody for use in a method of enhancing the elimination of C5 from plasma in an individual, the method comprising administering an effective amount of the anti-C5 antibody to the individual to enhance the elimination of C5 from plasma. In one embodiment, the anti-C5 antibody enhances the elimination of C5 from plasma compared to conventional anti-C5 antibodies that do not have pH-dependent binding properties. According to any of the above embodiments, the "individual" is preferably a human. In some other embodiments, the invention provides a primary anti-C5 antibody for inhibiting the accumulation of C5 in plasma. In some specific embodiments, the invention provides a primary anti-C5 antibody used in a method of inhibiting the accumulation of C5 in plasma in an individual, the method comprising administering an effective amount of the anti-C5 antibody to the individual to inhibit the accumulation of C5 in plasma. In one embodiment, the accumulation of C5 in plasma is a result of antigen-antibody complex formation. In another embodiment, the anti-C5 antibody inhibits the accumulation of C5 in plasma compared to conventional anti-C5 antibodies that do not have pH-dependent binding properties. According to any of the above embodiments, the "individual" is preferably a human. The anti-C5 antibody of this invention can inhibit C5 activation. In some other embodiments, the invention provides an anti-C5 antibody for inhibiting C5 activation. In some specific embodiments, the invention provides an anti-C5 antibody for use in a method of inhibiting C5 activation in an individual, the method comprising administering an effective amount of the anti-C5 antibody to the individual to inhibit C5 activation. In one embodiment, C5-regulated cytotoxicity is inhibited by inhibiting C5 activation. According to any of the above embodiments, the "individual" is preferably a human. In yet another embodiment, the present invention provides the use of anti-C5 antibodies in the production or preparation of pharmaceuticals. In one embodiment, the pharmaceutical is for the treatment of a complement regulation disease or condition involving excessive or uncontrolled C5 activation. In yet another embodiment, the pharmaceutical is a method of treating a complement regulation disease or condition involving excessive or uncontrolled C5 activation, comprising administering an effective amount of the pharmaceutical to an individual having a complement regulation disease or condition involving excessive or uncontrolled C5 activation. In such an embodiment, the method further comprises administering an effective amount of at least one additional therapeutic agent to the individual. The "individual" according to any of the above embodiments is preferably a human being. In another embodiment, the drug is used to enhance the elimination of C5 from plasma. In yet another embodiment, the drug is a method for enhancing the elimination of C5 from plasma in an individual, the method comprising administering an effective amount of the drug to the individual to enhance the elimination of C5 from plasma. In one embodiment, an anti-C5 antibody enhances the elimination of C5 from plasma compared to conventional anti-C5 antibodies that do not have pH-dependent binding properties. According to any of the above embodiments, the "individual" may be a human. In another embodiment, the drug is used to inhibit the accumulation of C5 in plasma. In yet another embodiment, the drug is a method for inhibiting the accumulation of C5 in plasma in an individual, the method comprising administering an effective amount of the drug to the individual to inhibit the accumulation of C5 in plasma. In one embodiment, the accumulation of C5 in plasma is a result of antigen-antibody complex formation. In another embodiment, an anti-C5 antibody inhibits the accumulation of C5 in plasma, compared to conventional anti-C5 antibodies that do not have pH-dependent binding properties. According to any of the above embodiments, the "individual" may be a human. The anti-C5 antibody of this invention can inhibit C5 activation. In another embodiment, the drug is used to inhibit C5 activation. In yet another embodiment, the drug is a method for inhibiting C5 activation in an individual, the method comprising administering an effective amount of the drug to the individual to inhibit C5 activation. In one embodiment, C5-regulated cytotoxicity can be inhibited by inhibiting C5 activation. According to any of the above embodiments, the "individual" can be a human. In yet another embodiment, the present invention provides a method for treating complement regulation disorders or conditions involving excessive or uncontrolled C5 activation. In one embodiment, the method includes administering an effective amount of an anti-C5 antibody to an individual having said complement regulation disorder or condition involving excessive or uncontrolled C5 activation. In such an embodiment, the method further includes administering an effective amount of at least one additional therapeutic agent to the individual. An “individual” according to any of the above embodiments may be a human being. In another embodiment, the invention provides a method for enhancing the elimination of C5 from plasma in an individual. In one embodiment, the method comprises administering an effective amount of an anti-C5 antibody to the individual to enhance the elimination of C5 from plasma. In one embodiment, the anti-C5 antibody enhances the elimination of C5 from plasma compared to conventional anti-C5 antibodies that do not possess pH-dependent binding properties. In one embodiment, the "individual" is a human being. In another embodiment, the invention provides a method for inhibiting the accumulation of C5 in plasma in an individual. In one embodiment, the method comprises administering an effective amount of an anti-C5 antibody to the individual to inhibit the accumulation of C5 in plasma. In one embodiment, the accumulation of C5 in plasma is a result of antigen-antibody formation. In another embodiment, the anti-C5 antibody inhibits the accumulation of C5 in plasma compared to conventional anti-C5 antibodies that do not possess pH-dependent binding properties. In one embodiment, the "individual" is a human being. The anti-C5 antibody of the present invention can inhibit C5 activation. In another embodiment, the invention provides a method for inhibiting C5 activation in an individual. In one embodiment, the method comprises administering an effective amount of anti-C5 antibody to an individual to inhibit C5 activation. In one embodiment, C5-regulated cytotoxicity can be inhibited by inhibiting C5 activation. According to any of the above embodiments, "individual" is a human being. In yet another embodiment, the present invention provides a pharmaceutical formulation comprising any of the anti-C5 antibodies provided herein, for example, for any of more than one therapeutic method. In one embodiment, the pharmaceutical formulation comprises any of the anti-C5 antibodies provided herein and a pharmaceutically acceptable carrier. In another embodiment, the pharmaceutical formulation comprises any of the anti-C5 antibodies provided herein and at least one additional therapeutic agent. In another embodiment, the pharmaceutical formulation is used for the treatment of complement regulation diseases or conditions involving excessive or uncontrolled C5 activation. In yet another embodiment, the pharmaceutical formulation is used to enhance the elimination of C5 from plasma. In one embodiment, an anti-C5 antibody enhances the elimination of C5 from plasma compared to conventional anti-C5 antibodies that do not have pH-dependent binding properties. In yet another embodiment, the pharmaceutical formulation is used to inhibit the accumulation of C5 in plasma. In one embodiment, the accumulation of C5 in plasma is a result of antigen-antibody complex formation. In another embodiment, an anti-C5 antibody inhibits the accumulation of C5 in plasma compared to conventional anti-C5 antibodies that do not have pH-dependent binding properties. The anti-C5 antibody of the present invention can inhibit C5 activation. In yet another embodiment, the pharmaceutical formulation is used to inhibit C5 activation. In one embodiment, C5-regulated cytotoxicity is inhibited by inhibiting C5 activation. In one embodiment, the pharmaceutical formulation is administered to an individual having a complement regulation disease or condition involving excessive or uncontrolled C5 activation. The "individual" according to any of the above embodiments is preferably a human being. In one state, individuals possess wild-type C5. In another state, individuals possess a C5 variant. In certain embodiments, the C5 variant has similar biological activity to wild-type C5. Such C5 variants may comprise at least one variant selected from the group consisting of V145I, R449G, V802I, R885H, R928Q, D966Y, S1310N, and E1437D. Herein, R885H, for example, represents a genetic variant in which arginine at position 885 is replaced by histidine. In another embodiment, the present invention provides a method for preparing a drug or pharmaceutical formulation, comprising mixing any of the anti-C5 antibodies provided herein with a pharmaceutically acceptable carrier, for example, for use in any of the above-described treatment methods. In one embodiment, the method for preparing a drug or pharmaceutical formulation further comprises adding at least one additional therapeutic agent to the drug or pharmaceutical formulation. In some specific embodiments, complement regulation diseases or conditions involving excessive or uncontrolled C5 activation are selected from the group consisting of: rheumatoid arthritis (RA); systemic lupus erythematosus (SLE); lupus nephritis; ischemia-reperfusion injury (IRI); asthma; paroxysmal nocturnal hemoglobinuria (PNH); hemolytic uremic syndrome (HUS) (e.g., atypical hemolytic uremic syndrome (aHUS)); dense deposit disease (DDD); neuromyelitis optica (NMO); multifocal motor neuropathy (MMN); and multiple sclerosis. MS; Systemic sclerosis; Macular degeneration (e.g., age-related macular degeneration (AMD)); Hemolysis, elevated liver enzymes, and HELLP syndrome; Thrombotic thrombocytopenic purpura (TPP); Spontaneous fetal loss; Epidermolysis bullosa; Recurrent fetal loss; Preeclampsia; Traumatic brain injury; Myasthenia gravis; Cold agglutinin syndrome; Sjögren's syndrome; Dermatomyositis; Bullous pemphigoid; Phototoxic reaction; Shiga toxin-associated hemolytic uremic syndrome. E. coli-related hemolytic uremic syndrome; typical or infectious hemolytic uremic syndrome (tHUS); C3 glomerulonephritis; anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis; humoral and vascular transplant rejection; acute antibody-mediated rejection (AMR); graft dysfunction; myocardial infarction; allogeneic transplantation; sepsis; coronary artery disease; hereditary angioedema; dermatomyositis; Graves' disease; atherosclerosis; Alzheimer's disease (AD); Huntington's disease; Creutzfeld-Jacob's disease; Parkinson's disease. Disease; Cancer; Wound; Septic shock; Spinal cord injury; Uveitis; Diabetic retinopathy; Retinopathy of prematurity; Glomerulonephritis; Membranous nephritis; Immunoglobulin A nephropathy; Adult respiratory distress syndrome (ARDS); Chronic obstructive pulmonary disease (COPD); Cystic fibrosis; Hemolytic anemia; Paroxysmal cold hemoglobinuria; Anaphylactic shock; Allergy; Osteoporosis; Osteoarthritis; Hashimoto's thyroiditis; Type I diabetes; Psoriasis; Pemphigus; Autoimmune hemolytic anemia AIHA; idiopathic thrombocytopenic purpura (ITP); Goodpasture syndrome; Degos disease; antiphospholipid syndrome (APS);Catastrophic antiphospholipid syndrome (CAPS); cardiovascular disease; myocarditis; cerebrovascular disorder; peripheral vascular disease; renal vascular disease; mesenteric / enteric vascular disorder; vasculitis; Henoch-Schönlein purpura nephritis; Takayasu's disease; dilated cardiomyopathy; diabetic angiopathy; Kawasaki's disease (arteritis); venous gas embolus (VGE); restenosis following stent placement; rotational atherectomy; membranous nephropathy; Guillain-Barré syndrome (GBS); Fisher syndrome. Syndrome; antigen-induced arthritis; synovitis; viral infection; bacterial infection; fungal infection; and damage caused by myocardial infarction, cardiopulmonary bypass, and hemodialysis. In some specific embodiments, the disease or condition that complement regulation is an eye disease. In still other embodiments, the eye condition is macular degeneration. In yet another embodiment, the macular degeneration is age-related macular degeneration (AMD). In still yet another embodiment, the AMD is dry AMD. In some specific embodiments, the disease or condition of complement regulation is paroxysmal nocturnal hemoglobinuria (PNH). In some specific embodiments, the disease or condition that complement regulation is myocardial infarction. In some specific embodiments, the disease or condition that complement regulation is rheumatoid arthritis (RA). In some specific embodiments, the disease or condition that complement regulation is osteoporosis or osteoarthritis. In some specific embodiments, the disease or condition that complement regulation is inflammation. In some specific embodiments, the disease or condition that complement regulation is cancer. In treatment, the antibodies of the present invention can be used alone or in combination with other agents. For example, the antibodies of the present invention can be co-administered with at least one additional therapeutic agent. Combination therapies as described above involve combined administration (where two or more therapeutic agents are contained in the same or separate formulations) and separate administration. In this case, the administration of the antibody of the present invention can occur before, simultaneously with, and / or after the administration of additional therapeutic agents and / or reagents. In one embodiment, the administration of the anti-C5 antibody and the administration of additional therapeutic agents occur within approximately one month, or within approximately one, two, or three weeks, or within approximately one, two, three, four, five, or six days. The antibodies (and any additional therapeutic agents) of this invention can be administered by any suitable method, including parenteral, intrapulmonary, and intranasal administration, and, if local treatment is required, intralesional administration. Parenteral infusion includes intramuscular, intravenous, intra-arterial, intraperitoneal, or subcutaneous administration. Depending to some extent on whether the administration is short-term or long-term, it can be administered by any suitable route, such as by injection, for example, intravenous or subcutaneous injection. Various administration schedules are covered herein, including but not limited to single administration or multiple administrations at multiple time points, bolus administration, and pulsatile infusion. The antibodies of this invention will be formulated, dosed, and administered in a manner consistent with good medical practice. Factors considered in this context include the specific disease to be treated, the specific mammal to be treated, the individual patient's clinical condition, the cause of the disease, the location of reagent delivery, the method of administration, the timing of administration, and other factors known to the medical practitioner. The antibodies do not necessarily, but optionally, need to be formulated with one or more reagents currently used for the prevention or treatment of the problem disease. The effective amount of other reagents depends on the amount of antibody present in the formulation, the type of disease or treatment, and other factors discussed above. These are generally used at the same dosage and via the route of administration as described herein, or at about 1 to 99% of the dosage described herein, or at any dosage and route of administration determined empirically / clinically. For the prevention or treatment of disease, the appropriate dosage of the antibody of the present invention (when used alone or in combination with one or more other additional therapeutic agents) will depend on the type of disease to be treated, the type of antibody, the severity and progression of the disease, whether the antibody is administered for preventive or therapeutic purposes, previous treatments, the patient's clinical history and response to the antibody, and the judgment of the attending physician. The antibody is appropriately administered to the patient as a single treatment or in series of treatments. Depending on the type and severity of the disease, an antibody of about 1 μg / kg to 15 mg / kg (e.g., 0.1 mg / kg to 10 mg / kg) may be the initial candidate dose for administration to the patient, whether, for example, by single or multiple separate administrations, or by continuous infusion. A typical daily dose may be in the range of about 1 μg / kg to 100 mg / kg or more, depending on the factors mentioned above. For repeated administration for several days or longer, treatment will generally continue until the desired suppression of disease symptoms is achieved, depending on the condition. An exemplary dose of the antibody should be in the range of about 0.05 mg / kg to about 10 mg / kg. Therefore, one or more doses of approximately 0.5 mg / kg, 2.0 mg / kg, 4.0 mg / kg, or 10 mg / kg (or any combination thereof) may be administered to the patient. Such doses may be administered intermittently, for example weekly or every three weeks (e.g., to give the patient approximately 2 to approximately 20, or for example, approximately 6 doses of the antibody). An initial higher loading dose may be administered, followed by one or more lower doses. Progression of this therapy can be easily monitored using routine methods and assays. It should be understood that any of the above formulations or treatment methods can be implemented using the immunoconjugate of the present invention to replace or add to the anti-C5 antibody. F. Products In another embodiment of the invention, an article is provided comprising materials that can be used to treat, prevent, and / or diagnose the aforementioned conditions. The article includes a container and a label or package insert on or attached to the container. Suitable containers include, for example, bottles, vials, syringes, IV solution pouches, etc. The container may be made of various materials such as glass or plastic. The container contains a composition, which is used alone or in combination with another composition that is effective for treating, preventing, and / or diagnosing the condition, a composition effective for the treatment of symptoms, and may have a sterile access port (e.g., the container may have an intravenous solution bag or vial with a stopper that can be punctured by a hypodermic needle). At least one active agent in the composition is an antibody of the present invention. The label or package insert indicates that the composition is for the treatment of a specific condition. Furthermore, the article may comprise (a) a first container containing the composition therein, wherein the composition includes the antibody of the present invention; and (b) a second container containing the composition therein, wherein the composition includes additional cytotoxic agents or other therapeutic agents. In this embodiment of the invention, the article may further include a package insert indicating that the composition can be used to treat specific symptoms. Alternatively or additionally, the article may further include a second (or third) container, which includes pharmaceutically acceptable buffers such as sterile water for injection (BWFI), phosphate-buffered saline, Ringer's solution, and glucose solution. From a commercial and user perspective, it may also include other materials as required, including other buffers, diluents, filter membranes, needles, and syringes. It should be understood that any of the above-described products may contain the immunoconjugate of the present invention to replace or supplement anti-C5 antibodies. Examples The following are examples of the methods and compositions of the present invention. It should be understood that many other embodiments can be implemented based on the general description provided above. [Example 1] Preparation of C5 1.1. Expression and Purification of Recombinant Human and Rhesus Monkey C5 Recombinant human C5 was transiently expressed using the FreeStyle293-F cell line (Thermo Fisher, Carlsbad, CA, USA) (NCBI GenBank accession number: NP_001726.2, SEQ ID NO: 39). The conditioned medium for expressing human C5 was diluted with an equal volume of milliQ water and then used on a Q-sepharose FF or Q-sepharose HP anion exchange column (GE healthcare, Uppsala, Sweden), followed by elution with a NaCl gradient. Fractions containing human C5 were collected, and the salt concentration and pH were adjusted to 80 mM NaCl and pH 6.4, respectively. The resulting samples were used on an SP-sepharose HP cation exchange column (GE healthcare, Uppsala, Sweden) and eluted with a NaCl gradient. Fractions containing human C5 were collected and applied to a CHT ceramic hydroxyapatite column (Bio-Rad Laboratories, Hercules, CA, USA). The human C5 eluent was then used on a Superdex 200 colloidal filtration column (GE healthcare, Uppsala, Sweden). Fractions containing human C5 were collected and stored at -150°C. The expression and purification of recombinant rhesus monkey C5 (NCBI GenBank accession number: XP_005580972, SEQ ID NO: 44) were performed in the same manner as the human fraction. 1.2. Purification of rhesus monkey C5 (cynoC5) from plasma Plasma samples from rhesus monkeys were eluted with SSL7 agarose (Invivogen, San Diego, CA, USA) followed by elution with 100 mM sodium acetate, pH 3.5. The fraction containing cynoC5 was immediately neutralized and applied sequentially to a protein A HP column (GE healthcare, Uppsala, Sweden) and a peptide M agarose column (Invivogen, San Diego, CA, USA). The fractions were then processed using a Superdex 200 colloid filtration column (GE healthcare, Uppsala, Sweden). The fraction containing cynoC5 was collected and stored at -80°C. [Example 2] Production of anti-C5 antibodies 2.1. Antibody screening Anti-C5 antibodies were prepared, selected, and determined in the following manner: NZW rabbits aged 12 to 16 weeks were intradermally immunized with human C5 and / or monkey C5 (50-100 µg / dose / rabbit). This dose was repeated 4-5 times over a 2-month period. One week after the final immunization, spleens and blood were collected from immunized rabbits. Antigen-specific B cells were stained with labeled antigens and classified using an FCM cell classifier (FACS aria III, BD). Cells were then discretized at a density of 1 cell / well with 25,000 cells / well of EL4 cells in 96-well plates (European Collection of Cell Cultures). Activated rabbit T cell conditioned medium was diluted 20-fold and cultured for 7-12 days. EL4 cells were pretreated with mitomycin C (Sigma, Cat No. M4287) for 2 hours and washed 3 times. Rabbit T cell conditioned medium was prepared by culturing rabbit thymocytes in RPMI-1640 containing phytohemagglutinin-M (Roche, Cat No. 1 1082132-001), phorbol 12-myristate 13-acetate (Sigma, Cat No. P1585), and 2% FBS. After culture, B cell culture supernatant was collected for further analysis, and the precipitate was cryopreserved (pellet). The specificity of antibodies in B cell culture supernatant was tested using an ELISA assay. Biotin-coated plates (GeneScript, Cat No. Z02043) were coated with 50 nM PBS onto 384-well MAXISorp (Nunc, Cat No. 164688) and incubated at room temperature for 1 hour. Blocking One (Nacalai Tesque, Cat No. 03953-95) was then used to block the cells. Human or monkey C5 cells were labeled with NHS-PEG4-Biotin (PIERCE, Cat No. 21329) and added to the blocked ELISA plates. The cells were incubated for 1 hour and then washed. B cell culture supernatant was added to the ELISA plates, incubated for 1 hour, and then washed. Binding was detected by goat anti-rabbit IgG-horseradish peroxidase (BETHYL, Cat No. A120-111P) followed by ABTS (KPL, Cat No. 50-66-06). The pH-dependent binding of the antibody to C5 was assessed using an ELISA assay. Goat anti-rabbit IgG-Fc (BETHYL, Cat No. A120-111A), diluted to 1 µg / ml with PBS(-), was added to 384 wells of MAXISorp (Nunc, Cat No. 164688) and incubated at room temperature for 1 hour, followed by blocking with a 5-fold dilution of Blocking One (Nacalai Tesque, Cat No. 03953-95). After incubation, the plates were washed and B cell culture supernatant was added. The plates were incubated for 1 hour, washed, and then 500 pM biotinylated human or monkey C5 was added and incubated for another 1 hour. After incubation, the plates were washed and incubated with pH 7.4 MES buffer (20 mM MES, 150 mM NaCl, and 1.2 mM CaCl₂). 2) Incubate in pH 5.8 MES buffer (20 mM MES, 150 mM NaCl, and 1 mM EDTA) at room temperature for 1 hour. After incubation, ABTS (KPL, Cat No. 50-66-06) is added to detect the binding of biotinylated C5 using a biotin-horseradish peroxidase conjugate (Thermo Scientific, Cat No. 21132). The Octet RED384 system (Pall Life Sciences) was used to evaluate the affinity and pH-dependent binding of antibodies to C5. Antibodies secreted from B cell culture supernatant were mounted on protein A biosensor probes (Pall Life Sciences) and immersed in 50 nM human or monkey C5 in pH 7.4 MES buffer to analyze binding kinetics. Dissociation kinetics were analyzed in both pH 7.4 and pH 5.8 MES buffers. A total of 41,439 B cell lines were screened for affinity and pH-dependent binding to human or monkey C5, and 677 lines were selected and designated as CFA0001-0677. RNA from the selected cell lines was purified from cryopreservation precipitates using the ZR-96 Quick-RNA kit (ZYMO RESEARCH, Cat No. R1053). DNA encoding the antibody heavy chain variable region in the selected cell lines was amplified by reverse transcription PCR and recombinated with DNA encoding the F760G4 (Sequence Identification Number: 33) or F939G4 (Sequence Identification Number: 34) heavy chain constant region. DNA encoding the antibody light chain variable region was amplified by reverse transcription PCR and recombinated with DNA encoding the k0MTC light chain constant region (Sequence Identification Number: 36). Separately, the heavy and light chain genes of the existing humanized anti-C5 antibody, eculizumab (EcuH-G2G4, sequence number: 29 and EcuL-k0, sequence number: 30), were synthesized. The DNA encoding VH (EcuH, sequence number: 31) was fused in-frame into DNA encoding modified human IgG4 CH (F760G4, sequence number: 33), and the DNA encoding VL (EcuL, sequence number: 32) was fused in-frame into DNA encoding the k0 light chain constant region (sequence number: 37). Each fused coding sequence was transfected into an expression vector. The antibody was expressed in FreeStyle™ 293-F cells (Invitrogen) and purified from the culture supernatant to assess functional activity. The neutralizing activity of the antibody was assessed by testing for inhibition of complement activity using a liposome cytolysis assay as described in Example 5.1. 2.2. Epitope binning using sandwich ELISA Anti-C5 antibodies with high affinity, pH-dependent, or neutralizing activity were selected for further analysis. The selected antibodies were classified into different antigenic determinant compartments using a sandwich ELISA assay, binding to the same or overlapping antigenic determinants of the C5 protein. Unlabeled capture antibodies were diluted to 1 µg / mL with PBS(-) and added to 384-well MAXISorp discs (Nunc, Cat No. 164688). The discs were incubated at room temperature for 1 hour and blocked with a 5-fold dilution of Blocking One (Nacalai Tesque, Cat No. 03953-95). The discs were incubated for 1 hour, washed, and then 2 nM of human C5 was added and incubated for another 1 hour. After incubation, the discs were washed and labeled detection antibodies (1 µg / mL, biotinylated with NHS-PEG4-Biotin) were added. After 1 hour of incubation, ABTS (KPL, Cat No. 50-66-06) was added using a biotin-horseradish peroxidase conjugate (Thermo Scientific, Cat No. 21132) to detect the binding of the biotinylated antibody. All anti-C5 antibodies were used as both capture and detection antibodies, and were fully paired. As shown in Figure 1, competing antibodies were classified into seven antigenic determinant compartments: CFA0668, CFA0334, and CFA0319 were classified into antigenic determinant A; CFA0647, CFA0589, CFA0341, CFA0639, CFA0635, CFA0330, and CFA0318 were classified into antigenic determinant B; and CFA0538, CFA0501, CFA0599, and CFA0307 were classified into antigenic determinant B. CFA0366, CFA0305, CFA0675, CFA0666, and CFA0672 were classified into antigenic determinant C; eculizumab and CFA0322 were classified into antigenic determinant D; CFA0329 was classified into antigenic determinant E; CFA0359 and CFA0217 were classified into antigenic determinant F; and CFA0579, CFA0328, and CFA0272 were classified into antigenic determinant G. Figure 1 shows some of the antigenic determinant classifications for anti-C5 chimeric antibodies. Table 2 lists the VH and VL sequences of anti-C5 antibodies classified into antigenic determinant C. [Table 2] Anti-C5 antibodies classified into antigenic determinant C 2.3. Humanization and Optimization To reduce the potential immunogenicity of the antibody, some variable regions of the anti-C5 antibody were humanized. This was achieved using the conventional CDR grafting method. Nature 321:522-525 (1986) transplanted the complementarity-determining region (CDR) of the anti-C5 rabbit antibody into the homologous human antibody framework (FR). Genes encoding humanized VH and VL were synthesized and recombined with modified human IgG4 CH (SG402, sequence number: 35) and human CL (SK1, sequence number: 38), respectively, and the recombinant sequences were transfected into expression vectors. Mutations and combinations thereof were detected to identify those that improved the binding properties of some lead antibodies. Several mutations were then introduced into the humanized variable region to enhance the binding affinity for C5 at neutral pH or to decrease the binding affinity for C5 at acidic pH. One of the optimized variants, 305LO5 (VH, sequence number: 10; VL, sequence number: 20; HVR-H1, sequence number: 54; HVR-H2, sequence number: 64; HVR-H3, sequence number: 74; HVR-L1, sequence number: 84; HVR-L2, sequence number: 94; and HVR-L3, sequence number: 104), was thus derived from CFA0305. The antibody was expressed in HEK293 cells and purified using protein A, and the HEK293 cells were co-transfected with a mixture of heavy and light chain expression vectors. [Example 3] 3.1. Binding Characteristics of Anti-C5 Antibody Recombinant Antibody Expression and Purification The recombinant antibody was transiently expressed using the FreeStyle293-F cell line (Thermo Fisher, Carlsbad, CA, USA). Purification was performed from the conditioned medium containing the antibody using standard methods with protein A. Colloidal filtration was performed further as needed. 3.2. pH-Dependent Assessment USE BIACORE ® The T200 instrument (GE Healthcare) was used to evaluate the kinetic parameters of anti-C5 antibody against recombinant human C5 at 37°C and pH 7.4 and pH 5.8. ProA / G (Pierce) was immobilized on the CM4 sensor chip using an amine coupling kit (GE Healthcare) according to GE Healthcare's recommended settings. Antibodies and analytes were diluted in their respective electrophoresis buffers, ACES pH 7.4 and pH 5.8 (20 mM ACES, 150 mM NaCl, 1.2 mM CaCl₂). 2. 0.05% Tween 20. 0.005% NaN 3) Each antibody is captured on the sensing surface by ProA / G. The antibody capture level is typically 60-90 resonance units (RU). Then, recombinant human C5 is injected at concentrations of 10 and 20 nM or 20 and 40 nM, followed by dissociation. The surface is regenerated using 25 mM NaOH. (The last sentence appears to be incomplete and possibly refers to a process called BIACORE.) ® The T200 assessment software, version 2.0 (GE Healthcare), was used to fit the sensing map using a 1:1 binding model to determine kinetic parameters under two pH conditions. Figures 2A and 2B show the sensing maps for all antibodies. Table 3 lists the binding rate (ka), dissociation rate (kd), and binding affinity (KD) of the antibodies. All antibodies except CFA0330 (VH, sequence identifiers: 21 and VL, sequence identifiers: 25) and A0341 (VH, sequence identifiers: 22 and VL, sequence identifiers: 26) showed a relatively faster dissociation rate at pH 5.8 compared to pH 7.4. [Table 3] Kinetic parameters of anti-C5 antibodies at pH 7.4 and pH 5.8. 3.3. Cross-reactivity test To observe the cross-reactivity of anti-C5 antibodies against human C5 (hc5) and rhesus monkey C5 (cynoC5), BIACORE was performed. ® Kinetic assays. The assay setup was the same as described in Example 3.2, with recombinant cynoC5 injected at concentrations of 2, 10, and 50 nM. Kinetic parameters were determined using data fitting as described in Example 3.2. Table 4 lists the binding kinetics and affinity at pH 7.4. The kinetic parameters for hC5 shown in Table 4 are the results from Example 3.2. All anti-C5 antibodies except CFA0672 showed similar KD for both hC5 and cynoC5. CFA0672 showed an 8-fold weaker KD for cynoC5 compared to hC5. [Table 4] Binding kinetics and affinity of anti-C5 antibodies for hC5 and cynoC5 at pH 7.4 [Example 4] 4.1. Localization of Anti-C5 Antibody Antigen Determinants. The binding of anti-C5 MAb to the β-chain derivative peptide of C5 was tested using Western spectrophotometry. C5 peptides fused to the GST marker (pGEX-4T-1, GE Healthcare Life Sciences, 28-9545-49) were expressed in E. coli (DH5α, TOYOBO, DNA-903): 19-180, 161-340, 321-500, and 481-660. After incubation at 37°C for 5 hours with 1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG) and centrifugation at 20000×g for 1 minute to obtain the precipitate, the peptides were collected. E. coli samples. Precipitates were resuspended in sample buffer (2ME+) (Wako, 191-13272) and analyzed using Western spectrophotometry. Expression of individual peptides was confirmed using anti-GST antibody (Abcam, ab9085) (Figure 3). Arrows indicate GST-fused C5 peptides (46-49 kDa). Anti-C5 MAbs: CFA0305, CFA0307, ​​CFA0366, CFA0501, CFA0538, CFA0599, CFA0666, CFA0672, and CFA0675, bound to C5 domains 19-180 (Figure 3). 4.2. Expression and purification of the MG1-MG2 domains (1-225) of human C5. Recombinant MG1-MG2 domains of the human C5 β chain (Sequence Identification Number: 43) were transiently expressed using the FreeStyle293-F cell line (Thermo Fisher, Carlsbad, CA, USA). The conditioned medium expressing the MG1-MG2 domains was diluted with 1 / 2 volume of milliQ water and then used on a Q-agarose FF anion exchange column (GE healthcare, Uppsala, Sweden). The fraction flowing from the anion exchange column was adjusted to pH 5.0 and used on an SP-agarose HP cation exchange column (GE healthcare, Uppsala, Sweden) with a NaCl gradient elution. The fraction containing the MG1-MG2 domains was collected from the eluent and then applied to a Superdex 75 colloidal filter column equilibrated with 1x PBS (GE healthcare, Uppsala, Sweden). The fraction containing the MG1-MG2 domains was then pooled and stored at -80°C. 4.3. Binding Ability to the MG1-MG2 Domains The binding ability of anti-C5 antibodies to the MG1-MG2 domain was measured using the same assay setup as described in Example 3.2, except that the measurement was performed only at pH 7.4. The MG1-MG2 domain was injected at concentrations of 20 nM and 40 nM. As shown in Figure 4, all antibodies except eculizumab-F760G4 showed an increased binding response, indicating that these antibodies are MG1-MG2 binders. Eculizumab-F760G4, known as an α-chain binder, did not show binding to the MG1-MG2 domain. 4.4. Binding of anti-C5 MAb to C5 MG1-MG2 domain-derived peptides The binding of anti-C5 Mab to MG1-MG2 domain-derived peptides was tested in Western spectrophotometry. E. coli expressed C5 peptides fused to GST tags: 33-124, 45-124, 52-124, 33-111, 33-108, and 45-111 (sequence identification number: 40). After incubation with 1 mM IPTG at 37°C for 5 hours, and centrifugation at 20000×g for 1 minute to obtain the precipitate, the peptides were collected. E. coli samples. The precipitate was resuspended in sample buffer (2 ME+) and analyzed using Western spectrophotometry. Expression of the C5-derived peptide was confirmed with anti-GST antibody (Figure 5A). CFA0305 binds only to peptides 33-124 (Figure 5B). CFA0305 binds to the β-chain of recombinant human C5 (rhC5) (approximately 70 kDa), which was used as a control. Figure 5C summarizes the response of anti-C5 MAb to the C5-derived peptide. 4.5. Binding of anti-C5 MAb to C5 mutants Because crystal structure analysis predicted that three amino acid residues in the β chain of C5—E48, D51, and K109—are involved in the binding between C5 and anti-C5-MAb, the binding of C5 MAb to human C5 point mutants was analyzed in Western spectrophotometry. C5 point mutants were expressed in FS293 cells via lipid transfection, in which any of E48, D51, and K109 was replaced with alanine. Culture medium was collected 5 days after lipid transfection and subsequently used for Western spectrophotometry. SDS-PAGE was performed under reducing conditions, and the results are shown in Figure 6. Eculizumab binds to the α chain of wild-type (WT) C5 and the three C5 point mutants, while CFA0305 strongly binds to the β chain of WT C5, weakly binds to the β chain of the E48A C5 mutant, and does not bind to the β chains of the D51A and K109A C5 mutants. This indicates that these three amino acid residues are involved in antibody / antigen interactions. Table 5 summarizes the Western spectrophotometric analysis of anti-C5 MAb (CFA0305, CFA0307, ​​CFA0366, CFA0501, CFA0538, CFA0599, CFA0666, CFA0672, and CFA0675). Anti-C5 MAb were classified to the same antigenic determinant C, but the binding patterns between the antibodies differed slightly, suggesting that the binding regions of C5 against C5 MAb are close to each other but not identical. [Table 5] Summary of anti-C5 MAb responses to C5 mutants 4.6. Anti-C5 antibody and C5 mutant BIACORE ® Combined analysis To test whether residues E48, G51, and K109 are indeed involved in antibody / antigen interactions, BIACORE was performed. ® Combined analysis. Three C5 mutants: E48A, G51A, and K109A were prepared as described in Example 4.5. A culture supernatant sample containing mutant C5 overexpressed in FS293 cells was prepared at 40 µg / ml. For BIACORE ® Combined analysis, the sample was treated with BIACORE. ® The electrophoresis buffer (ACES pH 7.4, 10 mg / ml BSA, 1 mg / ml carboxymethyl dextran) was diluted 10-fold to achieve a final sample concentration of 4 µg / ml for mutant C5. Using the measurement conditions described in Example 3.2, with BIACORE ®The T200 instrument (GE Healthcare) was used at 37°C to evaluate the interaction between three C5 mutants and anti-C5 antibodies. ACES pH 7.4 buffer containing 10 mg / ml BSA and 1 mg / ml carboxymethyl dextran was used as the electrophoresis buffer. Eculizumab-F760G4 and 305LO5 were captured by monoclonal mouse anti-human IgG and Fc fragment-specific antibodies (GE Healthcare) on different flow cells. Flow cell 1 was used as a reference surface. Wild-type and mutant C5 proteins were injected onto the sensing surface at a concentration of 4 µg / ml to interact with the captured antibodies. At the end of each analysis cycle, 3M MgCl₂ was used as the electrophoresis buffer. 2. Regeneration of the sensing surface. Results were analyzed using Bia Evaluation software, version 2.0 (GE Healthcare). The curves of the reference flow path (flow path 1) and the blank injection of electrophoresis buffer were subtracted from the curves of the flow path with the capture antibody. As shown in Figure 7, all three C5 mutants can bind to eculizumab with a similar binding profile to wild-type C5. Regarding 305LO5, all three mutants showed a lower binding response to 305LO5 compared to wild-type C5. 305LO5 reduced the binding of D51A and K109A mutant C5 to baseline levels. 4.7. Identification of His residues on C5 that facilitate anti-C5 antibody and pH-dependent interactions between C5s. Crystal structure analysis revealed that three histidine residues on human C5 are located at the antibody / antigen interface. Histidine residues with a typical pKa of approximately 6.0 are known to contribute to pH-dependent protein-protein interactions (Igawa et al.). Biochim Biophys Acta 1844(11):1943-1950 (2014)). To investigate which His residue at the antibody / antigen interface contributes to the pH-dependent interaction between the anti-C5 antibody and C5, BIACORE was performed. ® Combined with assays. Three human C5 mutants with single His mutations (H70Y, H72Y, and H110Y) and a mutant with double His mutations (H70Y + H110Y) were prepared as follows: A single His mutant in which any of H70, H72, and H110 is substituted with tyrosine, and a double His mutant in which both H70 and H110 are substituted with tyrosine, were expressed in FS293 cells via lipid transfection. This was achieved using BIACORE modified as described in Example 4.6. ®The antigen-binding properties of the C5 His mutant to 305LO5, pH-dependent anti-C5 antibody were determined. In short, the antigen-binding properties were determined immediately after dissociation at pH 7.4 in BIACORE. ® An additional dissociation phase at pH 5.8 was added to the assay to assess the pH-dependent dissociation between the antibody and the antigen from the complex formed at pH 7.4. Scrubber 2.0 (BioLogic Software) was used to process and fit the data to determine the dissociation rate at pH 5.8. As shown in Figure 8, the single-His mutant and double-His mutant (H70 + H110) of C5 at H70 or H110 did not affect the binding of C5 to 305LO5 at neutral pH. Meanwhile, the single-His mutant at H72 showed a significant reduction in C5 binding to 305LO5. The dissociation rates of C5 His mutant and C5-wt proteins at pH 5.8 are shown in Table 6. As shown in Table 6, among the tested C5 antigens, C5-wt showed the fastest dissociation from 305LO5 at pH 5.8. Compared to C5-wt, the single-His mutant at H70 showed almost twice the slowest dissociation rate at pH 5.8, while the single-His mutant at H110 caused a slightly slower dissociation rate at pH 5.8. The double-His mutants at H70 and H110 had a greater impact on pH-dependent binding, exhibiting a dissociation rate almost three times slower than C5-wt at pH 5.8. [Table 6] Dissociation rate of His mutants to 305LO5 at pH 5.8 [Example 5] 5.1. Inhibition of Complement Activation by Anti-C5 MAb on Liposome Cell Lysis The inhibitory activity of anti-C5 MAb on complement activation was tested by a liposome lysis assay. 30 µL of normal human serum (6.7%) (Biopredic, SER018) was mixed with 20 µL of diluted MAb in a 96-well dish and incubated at 25°C on a shaker for 30 min. Liposomes sensitized with an antibody against dinitrophenyl (Autokit CH50, Wako, 995-40801) were transferred to each well, and the dish was incubated at 25°C on a shaker for 2 min. 50 µL of matrix solution (Autokit CH50) was added to each well and mixed by shaking at 25°C for 2 min. The final mixture was incubated at 37°C for 40 min, after which the OD of the mixture at 340 nm was measured. The percentage of liposome lysis was defined as 100 × [(OD...]]. MAb – OD 血清及脂質體背景 )] / [(OD 沒有 MAb – OD 血清及脂質體背景 Figure 9A shows that anti-C5 mabs: CFA0305, 0307, ​​0366, 0501, 0538, 0599, 0666, 0672, and 0675 inhibited liposome cell lysis. Two pH-independent antibodies, CFA0330 and 0341, also inhibited cell lysis (Figure 9B). 5.2. Inhibition of C5a formation by anti-C5 mabs During liposome lysis, C5a generation was tested with anti-C5 MAb to confirm that anti-C5 MAb inhibits C5 cleavage into C5a and C5b. The level of C5a in the supernatant from the liposome lysis assay was quantified using a C5a ELISA kit (R&D system, DY2037). All MAbs dose-dependently inhibited C5a generation in the supernatant (Figures 10A and 10B). 5.3. Inhibition of complement-activated hemolysis by anti-C5 MAb The inhibition of classical complement activity by anti-C5 MAb was tested in a hemolysis assay. The assay used a solution containing 0.5 mM MgCl₂. 2 and 0.15 mM CaCl Chicken red blood cell (cRBCs) were washed with gelatin / veronal buffered saline (GVB++) (Boston BioProducts, IBB-300X) (Innovative research, IC05-0810), followed by sensitization at 4°C for 15 minutes with 1 µg / ml anti-chicken RBC antibody (Rockland 103-4139). The cells were then washed with GVB++ and sensitized at 5 × 10⁻⁶ cells / ml. 7 Cells / ml were suspended in the same buffer. In separate round-bottom 96-well microplates, 50 µl of normal human serum (20%) (Biopredic, SER019) was mixed with 50 µl of diluted Mab and incubated at 37°C on a shaker for 30 min. Then, 60 µl of sensitized cRBC supernatant was added to the wells containing the serum, and the antibody mixture was incubated at 37°C for 30 min. After incubation, the plate was centrifuged at 1000×g for 2 min at 4°C. 100 µl of the supernatant was transferred to the wells of a flat-bottom 96-well microplate for OD measurement at 415 nm, with 630 nm as the reference wavelength. The percentage of hemolysis was defined as 100 × [(OD MAb – OD 血清及 cRBC )] / [(OD 沒有 MAb – OD 血清及 cRBC 背景 Figure 11 shows that anti-C5 Mab: CFA0305 and 305LO5 inhibit the hemolytic reaction of cRBCs. 5.4. Inhibition of the alternative complement pathway by anti-C5 MAb The alternative route hemolysis assay was performed in a manner similar to the classical route. Blood collected from New Zealand white rabbits (InVivos) was mixed with an equal volume of Alsever's solution (Sigma, A3551), and the mixture was used as rabbit RBCs (rRBCs). The assay was performed using 2 mM MgCl₂. GVB supplemented with 2 and 10 mM EGTA cleansed rRBCs, and at 7 × 10 8 Cells / ml were suspended in the same buffer. In a round-bottom 96-well microplate, 40 µl of normal human serum (25%) (Biopredic, SER019) was mixed with 40 µl of diluted Mab and incubated at 37°C on a shaker for 30 min. Then, 20 µl of rRBC supernatant was added to the wells containing the serum, and the antibody mixture was incubated at 37°C for 60 min. After incubation, the plate was centrifuged at 1000×g for 2 min at 4°C. The supernatant (70 µl) was transferred to the wells of a flat-bottom 96-well microplate for OD measurement at 415 nm, with 630 nm as the reference wavelength. Figure 12 shows that anti-C5 Mab: CFA0305 and CFA0672 inhibited the hemolytic reaction of rRBCs, representing the inhibition of the alternative complement pathway by these antibodies. [Example 6] 6.1. In vivo testing in C57BL / 6 mice: The in vivo pharmacokinetics of human C5 (Calbiochem) and anti-human C5 antibody were evaluated after administration of human C5 alone or human C5 and anti-human C5 antibody to C57BL / 6 mice (In Vivos or Biological Resource Centre, Singapore). Human C5 solution (0.01 mg / ml) or solutions containing human C5 and anti-human C5 antibodies (0.01 mg / ml and 2 mg / ml (CFA0305-F760G4, CFA0307-F760G4, CFA0366-F760G4, CFA0501-F760G4, CFA0538-F760G4, CFA0599-F760G4, CFA0666-F760G4, CFA0672-F760G4 and CFA0675-F760G4) or 0.2 mg / ml (CFA0330-F760G4 and CFA0341-F760G4, respectively) are administered via a single dose of 10 ml / kg into the tail vein. In this case, the anti-human C5 antibody was present in excess of human C5, therefore it can be assumed that almost every human C5 cell bound to the antibody. Blood was collected at 5 minutes, 7 hours, 1 day, 2 days, 3 days, and 7 days after administration. The collected blood was immediately centrifuged at 14,000 rpm and 4°C for 10 minutes to separate the plasma. The separated plasma was stored at -80°C before assay. The anti-human C5 antibodies used were CFA0305-F760G4, CFA0307-F760G4, CFA0330-F760G4, CFA0341-F760G4, CFA0366-F760G4, CFA0501-F760G4, CFA0538-F760G4, CFA0599-F760G4, CFA0666-F760G4, CFA0672-F760G4, and CFA0675-F760G4. 6.2. Total human C5 plasma concentration was measured by electrochemiluminescence (ECL) analysis. Measuring total human C5 concentration in mouse plasma using ECL When CFA0330-F760G4, CFA0341-F760G4, or human C5 alone is present in plasma samples, the following method is used. Anti-human C5 antibody (Santa Cruz) is dispensed onto MULTI-ARRAY 96-well bare plates (Meso Scale Discovery) and incubated overnight at 4°C to prepare plates immobilized with anti-human C5. Calibration curve samples and mouse plasma samples are prepared by diluting the antibody (CFA0330-F760G4 or CFA0341-F760G4) 100-fold or more at 1 µg / ml injection and incubated at 37°C for 30 minutes. Next, the samples are dispensed onto the plates immobilized with anti-human C5 and incubated at room temperature for 1 hour. Then, SULFO-TAG-labeled anti-human IgG antibody (Meso Scale Discovery) is added and reacted at room temperature for 1 hour, followed by washing. Immediately afterwards, a Read Buffer T (x4) (Meso Scale Discovery) was allocated and measurements were performed using a Sector Imager 2400 (Meso Scale Discovery). In cases where CFA0305-F760G4, CFA0307-F760G4, CFA0366-F760G4, CFA0501-F760G4, CFA0538-F760G4, CFA0599-F760G4, CFA0666-F760G4, CFA0672-F760G4, or CFA0675-F760G4 are present in plasma samples, the following method is used: Anti-human C5 antibody (CFA0329-F939G4; VH, SEQ ID NO: 23 and VL, SEQ ID NO: 27) is dispensed onto MULTI-ARRAY 96-well bare discs (Meso Scale Discovery) and incubated overnight at 4°C to prepare discs immobilized with anti-human C5. Calibration curve samples and mouse plasma samples were prepared by diluting them 100-fold or more with acidic solution (pH 5.5) and incubating at 37°C for 30 minutes. The samples were then aliquoted onto plates immobilized with anti-human C5 and incubated at room temperature for 1 hour. Next, SULFO-TAG-labeled anti-human C5 antibodies (CFA0300-F939G4; VH, SEQ ID NO: 24 and VL, SEQ ID NO: 28) were added and reacted at room temperature for 1 hour, followed by washing. Read Buffer T (x4) (Meso Scale Discovery) was then immediately dispensed and measured using a Sector Imager 2400 (Meso Scale Discovery). Human C5 concentrations were calculated using the analysis software SOFTmax PRO (Molecular Devices) based on the response to the calibration curve. The time-series of plasma human C5 concentrations after intravenous administration, measured by this method, is shown in Figure 13. The data are plotted as the percentage remaining compared to the plasma human C5 concentration at 5 minutes. 6.3. Measurement of Anti-Human C5 Antibody Plasma Concentrations by ECL Analysis The concentration of anti-human C5 antibody in mouse plasma was measured using ECL. Anti-human IgG (γ-chain specific) F(ab')2 antibody fragment (Sigma) or anti-human IgG κ chain antibody (Antibody Solutions) was dispensed onto MULTI-ARRAY 96-well bare plates (Meso Scale Discovery) and incubated overnight at 4°C to prepare plates immobilized with anti-human IgG. Calibration curve samples and mouse plasma samples were prepared at 100-fold or higher dilutions. The samples were then dispensed onto the plates immobilized with anti-human IgG and incubated at room temperature for 1 hour. Next, biotinylated anti-human IgG antibody (Southernbiotech) or SULFO-TAG-labeled anti-human IgG Fc antibody (Southernbiotech) was added and reacted at room temperature for 1 hour, followed by washing. SULFO-TAG-labeled streptavidin was added only when using biotinylated anti-human IgG antibody, and reacted at room temperature for 1 hour, followed by washing. Immediately afterwards, Read Buffer T (x4) (Meso Scale Discovery) was dispensed and measurements were performed using a Sector Imager 2400 (Meso Scale Discovery). Anti-human C5 concentrations were calculated using the analysis software SOFTmax PRO (Molecular Devices) based on the response to the calibration curve. The time-series of plasma anti-human C5 antibody concentrations after intravenous administration, measured using this method, is shown in Figure 14. Data are plotted as the percentage remaining compared to the anti-human C5 antibody concentration at 5 minutes. 6.4. Effect of pH-dependent anti-human C5 antibody binding on in vivo elimination of human C5 pH-dependent anti-human C5 antibodies (CFA0305-F760G4, CFA0307-F760G4, CFA0366-F760G4, CFA0501-F760G4, CFA0538-F760G4, CFA0599-F760G4, CFA0666-F760G4, CFA0672-F760G4, and CFA0675-F760G4) and pH-independent anti-human C5 antibodies (CFA0330-F760G4 and CFA0341-F760G4) were tested in vivo, and the resulting plasma anti-human C5 antibody concentrations and plasma human C5 concentrations were compared. As shown in Figure 14, antibody exposure was comparable. During this process, compared to non-pH-dependent anti-human C5 antibodies, the elimination of human C5 was accelerated when pH-dependent anti-human C5 antibodies were administered simultaneously (Figure 13). [Example 7] Optimization of the anti-C5 monoclonal antibody (305 variant) involved introducing several mutations into the optimal variable region of the anti-C5 antibody 305LO5 to further improve its properties, resulting in optimal variable regions 305LO15, 305LO16, 305LO18, 305LO19, 305LO20, 305LO22, and 305LO23. The amino acid sequences of VH and VL of the 305 variant are listed in Tables 7 and 8, respectively. The gene encoding humanized VH binds to modified human IgG1 CH variant SG115 (sequence identification number: 114) and modified human IgG4 CH variant SG422 (sequence identification number: 115) or SG429 (sequence identification number: 116). The gene encoding humanized VL binds to human CL (SK1, sequence identification number: 38). Separately, the heavy chain and light chain genes encoding humanized anti-C5 antibodies, BNJ441 (BNJ441H, sequence number: 149; BNJ441L, sequence number: 150), were synthesized and transfected into expression vectors. The antibody was expressed in HEK239 cells and purified using protein A. The HEK293 cells were co-transfected with a combination of heavy and light chain expression vectors. [Table 7] VH amino acid sequence of the 305 variant. [Table 8] VL amino acid sequences of 305 variants [Example 8] Binding characteristics of anti-C5 antibody (305 variant) USE BIACORE ®The T200 instrument (GE Healthcare) was used to evaluate the kinetic parameters of anti-C5 antibodies against recombinant human C5 at 37°C under three different conditions: (1) binding and dissociation at pH 7.4, (2) binding and dissociation at pH 5.8, and (3) binding at pH 7.4 but dissociation at pH 5.8. ProA / G (Pierce) was immobilized on the CM1 sensor chip using an amine coupling kit (GE Healthcare) according to GE Healthcare's recommended settings. Antibodies and analytes under conditions (1) and (3) were diluted in ACES pH 7.4 buffer (20 mM ACES, 150 mM NaCl, 1.2 mM CaCl₂). 2. 0.05% Tween 20. 0.005% NaN In step 3), the antibody and analyte from condition (2) were diluted in ACES pH 5.8 buffer (20 mM ACES, 150 mM NaCl, 1.2 mM CaCl₂). 2. 0.05% Tween 20. 0.005% NaN 3) In the middle stage, each antibody is captured on the sensing surface by ProA / G. The antibody capture level is typically 60-90 resonance units (RU). Then, recombinant human C5, prepared by three-fold serial dilution, is injected at 3 to 27 nM or 13.3 to 120 nM, followed by dissociation. The surface is regenerated using 25 mM NaOH. Using BIACORE... ® The T200 assessment software, version 2.0 (GE Healthcare), used a 1:1 fit sensor map to determine kinetic parameters under conditions (1) and (2), and a 1:1 dissociation fit sensor map using the MCK model to determine the dissociation rate under condition (3). The pH dependence of all antibodies was expressed as a ratio of the dissociation rates under conditions (2) and (1). Binding rate (ka), dissociation rate (kd), binding affinity (KD), and pH dependence are listed in Table 9. Compared to pH 7.4, all antibodies showed faster dissociation rates at pH 5.8, and their pH dependence was approximately 20-fold. [Table 9] Kinetic parameters of anti-C5 antibodies at pH 7.4 and pH 5.8 USE BIACORE ®The T200 instrument (GE Healthcare) was used at 37°C to determine the binding affinity of anti-C5 antibodies (BNJ441, eculizumab, and the 305 variant) to recombinant human C5 at pH 7.4 and pH 5.8 to assess the effect of pH on antigen binding. Using an amine coupling kit (GE Healthcare), goat anti-human IgG (Fc) multiclonal antibodies (KPL #01-10-20) were immobilized on a CM4 sensor chip according to the supplier's recommended settings. Antibodies and analytes were diluted in a solution containing 20 mM ACES, 150 mM NaCl, and 1.2 mM CaCl₂. 2. 0.05% Tween 20 and 0.005% NaN 3% ACES pH 7.4 buffer or ACES pH 5.8 buffer. Antibodies are captured onto the sensor chip surface using an anti-Fc method, typically at a capture level of 50-80 resonance units (RU). Recombinant human C5 is prepared by 3-fold serial dilutions starting at 27 nM under assay conditions at pH 7.4, or by 3-fold serial dilutions starting at 135 nM under assay conditions at pH 5.8. The surface is regenerated using 20 mM HCl and 0.01% Tween 20. Data are processed and fitted using BiaEvaluation 2.0 software (GE Healthcare) at a 1:1 binding model. The binding affinity (KD) of BNJ441, eculizumab, and the 305 variant to recombinant human C5 at pH 7.4 and pH 5.8 is listed in Table 10. The 305 variant showed a (KD at pH 5.8) / (KD at pH 7.4) ratio of approximately 800, which is 8 times higher than that of BNJ441, whose (KD at pH 5.8) / (KD at pH 7.4) ratio is only 93. [Table 10] [Example 9] Inhibitory Activity of Anti-C5 Antibody (305 Variant) on C5 Activation 9.1. Inhibition of Complement Activation by Anti-C5 MAb on Liposome Cell Lysis The inhibitory effect of anti-C5 MAb on complement activity was tested by a liposome lysis assay. 30 µL of normal human serum (6.7%) (Biopredic, SER019) was mixed with 20 µL of diluted MAb in a 96-well dish and incubated at room temperature on a shaker for 30 min. Liposome solution sensitized with an antibody against dinitrophenyl (Autokit CH50, Wako, 995-40801) was transferred to each well, and the dish was incubated at 37°C on a shaker for 2 min. 50 µL of matrix solution (Autokit CH50) was added to each well and mixed by shaking at 37°C for 2 min. The final mixture was incubated at 37°C for 40 min, and then the OD was measured at 340 nm. The percentage of liposome lysis was defined as 100 × [(OD MAb – OD 血清及脂質體背景 )] / [(OD 沒有 MAb – OD 血清及脂質體背景 Figure 15 shows that anti-C5 Mabs: 305LO15-SG422, 305LO16-SG422, 305LO18-SG422, 305LO19-SG422, 305LO20-SG422, and 305LO20-SG115 inhibit liposome lysis. Two antibodies with Fc variants, 305LO15-SG115 and 305LO23-SG429, also inhibit liposome lysis (Figure 16). The inhibitory effect of anti-C5 MAb on recombinant human C5 (Sequence Identification Number: 39) was tested. In a 96-well plate, 10 μL of C5-deficient human serum (Sigma, C1163) was mixed with 20 μL of diluted MAb and 20 μL of recombinant C5 (0.1 µg / mL) and incubated at 37 °C on a shaker for 1 hour. Liposomes (Autokit CH50) were transferred to each well and incubated at 37 °C on a shaker for 2 minutes. 50 μL of matrix solution (Autokit CH50) was added to each well and mixed by shaking at 37 °C for 2 minutes. The final mixture was incubated at 37 °C for 180 minutes, after which the OD was measured at 340 nm. The percentage of liposome cell lysis was as defined above. Figure 17 shows that anti-C5 MAbs: 305LO22-SG115, 305LO22-SG422, 305LO23-SG115, and 305LO23-SG422 inhibit liposome cell lysis. 9.2. Inhibition of C5a generation by anti-C5 MAbs During liposome lysis, C5a generation was tested against anti-C5 MAb to confirm that anti-C5 MAb inhibited C5 cleavage into C5a and C5b. The level of C5a in the supernatant from the liposome lysis assay was quantified using a C5a ELISA kit (R&D system, DY2037). All MAbs inhibited C5a generation in the supernatant in a dose-dependent manner (Figures 18 and 19). 9.3. Measurement of complement activity in rhesus monkey plasma. The inhibitory effect of anti-C5 MAb on complement activity was measured in rhesus monkey plasma. Anti-C5 Mab was administered orally to monkeys (20 mg / kg), and plasma samples were collected periodically until day 56. The plasma was analyzed using 0.5 mM MgCl₂. 2 and 0.15 mM CaCl Chicken red blood cells (cRBCs) were washed with gelatin / veronal buffered saline (GVB++) (Boston BioProducts, IBB-300X) (Innovative Research, IC05-0810), followed by sensitization at 4°C for 15 minutes with 1 µg / ml anti-chicken RBC antibody (Rockland 103-4139). The cells were then washed with GVB++ and sensitized at 1×10⁻⁶. 8Cells / ml were suspended in the same buffer. Monkey plasma sensitized with cRBCs was cultured at 37°C for 20 min in separate round-bottom 96-well microplates. After culture, the plates were centrifuged at 1000×g for 2 min at 4°C. The supernatant was transferred to the wells of a flat-bottom 96-well microplate to measure OD at 415 nm, with 630 nm as the reference wavelength. The percentage of hemolysis was defined as 100×[(OD 施用後 – OD 血漿及 cRBC 背景 )] / [(OD 施用前 – OD 血漿及 cRBC 背景 Figure 20 shows that anti-C5 MAb 305LO15-SG422, 305LO15-SG115, 305LO16-SG422, 305LO18-SG422, 305LO19-SG422, 305LO20-SG422, 305LO20-SG115, and 305LO23-SG115 inhibit complement activity in plasma. 9.4. Inhibition of the biological activity of anti-C5 MAb on C5 variants. The inhibitory effects of anti-C5 MAb on recombinant human C5 variants: V145I, R449G, V802I, R885H, R928Q, D966Y, S1310N, and E1437D were tested. PNH patients with the R885H mutation in C5 have been reported to have a poorer response to eculizumab (see, for example, Nishimura et al.). New Engl. J. Med. 370:632-639 (2014)). Various human C5 variants were expressed in FS293 cells, and the supernatant was used for subsequent studies. In 96-well plates, 10 μL of C5-deficient human serum (Sigma, C1163) was mixed with 20 μL of diluted Mab and 20 μL of cell culture medium containing recombinant C5 variants (2–3 µg / mL) and incubated at 37°C on a shaker for 0.5 h. Liposomes (Autokit CH50) were transferred to each well and incubated at 37°C on a shaker for 2 min. 50 μL of matrix solution (Autokit CH50) was added to each well and mixed by shaking at 37°C for 2 min. The final mixture was incubated at 37°C for 90 min, after which the OD was measured at 340 nm. The percentage of liposome cell lysis was as defined above. Figure 21 shows that anti-C5 MAb (eculizumab) did not inhibit the R885H C5 variant, but it did inhibit other tested variants. Figure 22 shows that anti-C5 Mab (305 variant) inhibited all tested C5 variants. 9.5. Inhibition of complement-activated liposome cytolysis by anti-C5 MAb The inhibition of complement activity by anti-C5 Mab was tested using a liposome lysis assay. 30 µL of normal human serum (6.7%) (Biopredic, SER019) was mixed with 20 µL of diluted MAb in a 96-well dish and incubated at room temperature on a shaker for 30 min. Liposomes sensitized with an antibody against dinitrophenyl (Autokit CH50, Wako, 995-40801) were transferred to each well, and the dish was incubated at 25°C on a shaker for 2 min. 50 µL of matrix solution (Autokit CH50) was added to each well and mixed by shaking at 25°C for 2 min. The final mixture was incubated at 37°C for 45 min, and then the OD was measured at 340 nm. The percentage inhibition of liposome lysis was defined as 100 × [(OD...]]. MAb – OD 血清及脂質體背景 )] / [(OD 沒有 MAb – OD 血清及脂質體背景Figure 13 shows that anti-C5 MAbs: 305LO15-SG422, 305LO16-SG422, 305LO18-SG422, 305LO19-SG422, 305LO20-SG422, and 305LO20-SG115 inhibit liposome lysis. Figure 23 shows that anti-C5 MAb, BNJ441, and the 305 variant inhibit liposome lysis, and the 305 variant has stronger inhibitory activity than BNJ441. [Example 10] Pharmacokinetic Study of Anti-C5 Monoclonal Antibody (305 Variant) in Rhesus Monkeys 10.1. In Vivo Assay Using Rhesus Monkeys The in vivo pharmacokinetics of the anti-human C5 antibody were assessed in rhesus monkeys (Shin Nippon Biomedical Laboratories, Ltd., Japan) after administration. A solution of the anti-human C5 antibody (2.5 mg / ml) was administered via cephalic vein in the forearm at a dose of approximately 8 ml / kg over 30 minutes. Blood was collected before administration and at 5 minutes, 7 hours, 1 day, 2 days, 3 days, 7 days, 14 days, 21 days, 28 days, 35 days, 42 days, 49 days, and 56 days after administration. Collected blood was immediately centrifuged at 1,700 × g and 4°C for 10 minutes to separate plasma. The separated plasma was stored at -70°C or below before assays. The preparation of the anti-human C5 antibody was as described in Example 7. 10.2. Measurement of total rhesus monkey C5 plasma concentration by ELISA The concentration of total rhesus monkey C5 in rhesus monkey plasma was measured by ELISA. The anti-human C5 antibody (in-house antibody produced using the method described in Example 2) was dispensed onto a Nunc-ImmunoPlate MaxiSorp (Nalge Nunc International) and incubated overnight at 4°C to prepare a plate immobilized with anti-rhesus monkey C5. Calibration curve samples and rhesus monkey plasma samples were prepared by diluting the antibody 20,000 times with 0.4 µg / ml injection and incubated at 37°C for 60 minutes. Then, the samples were dispensed onto the plate immobilized with anti-rhesus monkey C5 and incubated at room temperature for 1 hour. Next, HRP-labeled anti-human IgG antibody (Southernbiotech) was added and reacted at room temperature for 30 minutes, followed by washing. Then, ABTS ELISA HRP Substrate (KPL) was added. The signal was measured at a wavelength of 405 nm using a plate reader. Anti-rhesus monkey C5 concentrations were calculated using the analysis software SOFTmax PRO (Molecular Devices) based on the response to the calibration curve. The time-course of plasma rhesus monkey C5 concentrations after intravenous administration, measured using this method, is shown in Figure 24. The data are plotted as the percentage remaining compared to the pre-administration plasma rhesus monkey C5 concentration.Compared to pH-dependent anti-human C5 antibodies, pH-dependent anti-human C5 antibodies (305LO15-SG422, 305LO15-SG115, 305LO16-SG422, 305LO18-SG422, 305LO19-SG422, 305LO20-SG422, 305LO20-SG115, 305LO22-SG422, 305LO23-SG422, and 305LO23-SG115) showed decreased plasma C5 accumulation. 10.3. Plasma concentrations of anti-human C5 antibodies were measured by ELISA analysis. The concentration of anti-human C5 antibody in rhesus monkey plasma was measured by ELISA. Anti-human IgG κ-chain antibody (Antibody Solutions) was dispensed onto an unc-ImmunoPlate MaxiSorp (Nalge Nunc International) and incubated overnight at 4°C to prepare a plate immobilized with anti-human IgG. Calibration curve samples and rhesus monkey plasma samples were prepared at dilutions of 100-fold or more. The samples were then dispensed onto the plates immobilized with anti-human IgG and incubated at room temperature for 1 hour. HRP-labeled anti-human IgG antibody (Southernbiotech) was then added and reacted at room temperature for 30 minutes, followed by washing. ABTS ELISA HRP Substrate (KPL) was then added. The signal was measured at 405 nm using a plate reader. The concentration of anti-human C5 antibody was calculated using the analysis software SOFTmax PRO (Molecular Devices) based on the calibration curve response. The time-course of plasma anti-human C5 antibody concentration after intravenous administration, measured by this method, is shown in Figure 25. Compared to pH-independent anti-human C5 antibodies, pH-dependent anti-human C5 antibodies (305LO15-SG422, 305LO15-SG115, 305LO16-SG422, 305LO18-SG422, 305LO19-SG422, 305LO20-SG422, 305LO20-SG115, 305LO22-SG422, 305LO23-SG422, and 305LO23-SG115) exhibited longer half-lives. [Example 11] X-ray crystal structure analysis of Fab variant 305 and human C5-MG1 domain complex 11.1. Expression and purification of the MG1 domain (20-124) of human C5 Using pGEX-4T-1 vector (GE Healthcare), in In E. coli strain BL21 DE3 pLysS (Promega), protein expression was performed by fusing a thrombin-cleavable linker (GST-MG1) to a GST-tagged MG1 domain (amino residues 20-124 of sequence identification number 39). Protein expression was induced for 5 h at 25°C with 0.1 M m of isopropyl β-D-1-thiogalactopyranoside (IPTG). Bacterial cell pellets were dissolved in Bugbuster (Merck) supplemented with a mixture of lysonase (Merck) and complete protease inhibitors. GST-MG1 was then purified from the soluble fraction using a GSTrap column (GE Healthcare) according to the supplier's instructions. The GST tag was cleaved with thrombin (Sigma), and the resulting MG1 domain was further purified using a Superdex 75 colloidal filtration column (GE Healthcare). The fraction containing the MG1 domain was collected and stored at -80°C. 11.2. Preparation of the Fab fragment of the 305 variant The Fab fragment from one of the 305 optimal variants was prepared using conventional methods with papain (Roche Diagnostics, Cat No. 1047825). This was followed by loading onto a protein A column (MabSlect SuRe, GE Healthcare) to remove the Fc fragment, a cation exchange column (HiTrap SP HP, GE Healthcare), and a colloidal filtration column (Superdex200 16 / 60, GE Healthcare). Fractions containing the Fab fragment were collected and stored at −80°C. 11.3. Preparation of the 305 variant Fab and the human C5-MG1 domain complex. The purified recombinant human C5-MG1 domain was mixed with the purified 305 variant Fab fragment at a 1:1 molar ratio. The complex was purified by colloidal filtration chromatography (Superdex 200 10 / 300, GE Healthcare) using a column equilibrated with 25 mM HEPES, pH 7.5, and 100 mM NaCl. 11.4. Crystallization The purified complex was concentrated to approximately 10 mg / mL and crystallized at 4°C using a sitting drop vapor diffusion method combined with a seeding method. The storage solution consisted of 0.2 M magnesium formate and 15.0% w / v polyethylene glycol 3350. This successfully produced disc-shaped crystals within a few days. The crystals were then immersed in a solution of 0.2 M magnesium formate, 25.0% w / v polyethylene glycol 3350, and 20% glycerol. 11.5. Data Collection and Structure Determination X-ray diffraction data were measured at SPring-8 using a BL32XU. During the measurement, the crystal was continuously placed in a nitrogen gas flow at −178°C to maintain a frozen state, and the crystal was rotated 1.0° each time using an MX-225HS CCD detector (RAYONIX) attached to the X-ray beam, to collect a total of 180 X-ray diffraction images. The data was analyzed using the Xia2 program (…). J. Appl. Cryst.43:186-190 (2010), XDS Package ( Acta. Cryst. D66:125-132 (2010)) and Scala ( Acta. Cryst. D62:72-82 (2006) performed cell parameter determination, indexed diffraction points, and processed diffraction data from the acquired diffraction images, finally obtaining diffraction intensity data with a resolution of 2.11 Å. Crystal data statistics are shown in Table 11. [Table 11] Statistics on X-ray Data Collection and Improvement a; R merge = ∑ hkl∑ j| Ij( hkl) − < I( hkl)〉| / ∑ hkl∑ j| I( hkl)|,where Ij( hkl) and < I( hkl)〉 represents the measured intensity j and above The average intensity of reflection as indicated by the hkl index. R factor = ∑ hkl| F calc ( hkl)| − | F obs ( hkl)| / ∑ hkl| F obs ( hkl)|,where F obs and F calc These represent the observed and calculated structure factor amplitudes, respectively. R free The calculation is based on a 5% random reserved reflection. With the program Phaser ( J. Appl. Cryst. 40:658-674 (2007)) determined the structure by molecular substitution. The search model for the Fab domain was derived from the publicly available human IgG4 Fab crystal structure (PDB code: 1BBJ), and the search model for the MG1 domain was derived from the publicly available human C5 crystal structure (PDB code: 3CU7). Nat. Immunol. 9:753-760 (2008)). Using the Coot program ( The model was built using Acta Cryst. D66:486-501 (2010) and the program Refmac5 ( Improvements were observed in Acta Cryst. D67:355-367 (2011). The crystallization confidence factor (R) for diffraction intensity data in the range of 25–2.11 Å was 20.42%, with a Free R value of 26.44%. Statistical improvements in structure are shown in Table 11. 11.6. Overall structure of the Fab variant and the C5-MG1 domain complex of the 305 variant. The Fab sheet of the 305-optimized variant (“305 Fab”) is incorporated in a 1:1 ratio into the human C5-MG1 domain (“MG1”), and the asymmetric unit of the crystal structure contains two complexes, molecules 1 and 2, as depicted in Figure 26A. Molecules 1 and 2 can be aligned at 0.717 Å RMSD with Cα atoms in all residues, as shown in Figure 26B. The illustrations discussed below are prepared using molecule 1. In Figures 27A and 27B, the antigenic determinants of the 305 Fab contact region are located in the MG1 amino acid sequence and crystal structure, respectively. The antigenic determinants contain amino acid residues of MG1, and in the crystal structure, they include one or more atoms within 4.5 Å of any portion of the 305 Fab. Furthermore, antigenic determinants within 3.0 Å are emphasized in Figure 27A. 11.7. Interactions of E48, D51, and K109 As described in Examples 4.5 and 4.6, using Western dotting and BIACORE ® Combined analysis revealed that anti-C5 Mab containing the 305 antibody series binds to three human C5 point mutants: E48, D51, and K109. While the 305 variants strongly bind to WT C5, they bind only weakly to the E48A C5 mutant and not to the D51A or K109A mutants. The crystal structure of the 305 Fab and MG1 complex revealed that the three amino acids E48, D51, and K109 are all within 3.0 Å of 305 Fab, forming several hydrogen bonds with Fab, as shown in Figure 28A. A more detailed examination reveals that the K109 residue of MG1 is embedded in a groove at the interface of the heavy chain of Fab, and interacts tightly with Fab via three hydrogen bonds (H-CDR3_G97, H-CDR3_Y100, and H-CDR3_T100b) and via a salt bridge (H-CDR3_D95) (Figure 28D). D51 is located between the heavy chains of MG1 and 305 Fab, and forms two hydrogen bonds with H-CDR1_Ser32 and H-CDR2_Ser54 to fill the space (Figure 28C). These K109 and D51 residues, representing C5, are important residues for binding to the 305 antibody series. On the other hand, E48 is located closer to the surface and forms only one hydrogen bond with Fab, suggesting that its contribution to antibody binding is less than that of K109 and E51 (Figure 28B). These relationships are consistent with those of Western Ink and BIACORE in human C5 mutants. ® The results are consistent with the combined analysis (Examples 4.5 and 4.6). Additional note: The residue numbering of Fab amino acids follows the Kabat numbering framework (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991). 11.8. Interactions of H70, H72, and H110 in the human C5 and 305 antibody series. Crystal structure analysis revealed that three histidine residues on human C5, namely H70, H72, and H110, are contained in the antigenic determinant of variant 305 Fab, as shown in Figures 27A and 29A. (BIACORE performed) ®Combined analysis was conducted to investigate the contribution of these histidine residues to the pH-dependent protein-protein interactions between human C5 and the 305 variant Fab, which used human C5 mutants H70Y, H72Y, H110Y, and H70Y+H110Y (Example 4.7). H72Y resulted in the complete loss of binding to C5 by the 305 variant Fab. This residue of C5 is located in a pocket formed by the CDR2 loop of the heavy chain of 305 Fab and the loops of MG1 (L73, S74, and E76), and tightly fills this space, as shown in Figure 29C. Furthermore, the H72 residue of C5 forms a hydrogen bond with H-CDR2_Y58. The H72Y mutation was not expected to be tolerable because there was insufficient space to accommodate the large side chain of tyrosine, and the hydrogen bond with H-CDR2_Y58 could not be maintained. Regarding the pH-dependent contributions of H70 and H110, the H70Y and H110Y mutations result in a slower dissociation of the 305 variant Fab from C5 at pH 5.8. H70 forms an intramolecular hydrogen bond with T53 of MG1, which is thought to be disrupted at pH 5.8, and protonation of H70 at C5 leads to a conformational change in the corresponding portion of the interaction interface of MG1 (Figure 29B). Regarding H110, protonation of this C5 residue is expected to cause charge repulsion to the 305 Fab, which can be enhanced by protonation of the adjacent histidine residue H-CDR3_H100c (Figure 29D). While the foregoing invention has been described in detail by way of illustration and example for the purpose of clarity, such description and example should not be construed as limiting the scope of the invention. All patents and scientific literature cited herein are expressly incorporated herein by reference in their entirety. none [Figure 1] Figure 1 shows the epitope binning of the anti-C5 antibody, as described in Example 2.2. Antibodies classified into the same epitope binning are enclosed in thick lines. [Figure 2A] Figure 2A shows the biaxial structure of the anti-C5 antibody at pH 7.4 (solid line) and pH 5.8 (dashed line). ® Sensing patterns were used to assess pH dependence, as described in Example 3.2. CFA0305, CFA0307, ​​CFA0366, CFA0501, CFA0538, and CFA0599 are antibodies classified to antigenic determinant C, as described in Example 2.2. [Figure 2B] Figure 2B shows the BIACORE of anti-C5 antibodies at pH 7.4 (solid line) and pH 5.8 (dashed line). ®Sensing patterns were used to assess pH dependence, as described in Example 3.2. CFA0666, CFA0672, and CFA0675 are antibodies classified to antigenic determinant C, and CFA0330 and CFA0341 are antibodies classified to antigenic determinant B, as described in Example 2.2. 305LO5 is a humanized antibody to CFA0305, as described in Example 2.3. [Figure 3] Figure 3 shows a Western blotting analysis of the β-chain extension fragment (amino acids 19 to 180, 161 to 340, 321 to 500, and 481 to 660 at sequence identification number 40) of the C5 fusion with the GST label, as described in Example 4.1. CFA0305, CFA0307, ​​CFA0366, CFA0501, CFA0538, CFA0599, CFA0666, CFA0672, and CFA0675 are antibodies classified to antigenic determinant C. Anti-GST antibodies are the positive control group; the positions of the GST-fused C5 fragments (46 to 49 kDa) are indicated by arrows. [Figure 4] Figure 4 shows the biaxial region of the MG1-MG2 domain of the C5 β chain by the anti-C5 antibody. ®The sensing graph is as described in Example 4.3. The top column displays the results for CFA0305 (solid line), CFA0307 (dashed line), CFA0366 (dashed-dotted line), and eculizumab (dotted line). The middle column displays the results for CFA0501 (solid line), CFA0599 (dashed line), CFA0538 (dashed-dotted line), and eculizumab (dotted line). The bottom column displays the results for CFA0666 (solid line), CFA0672 (dashed line), CFA0675 (dashed-dotted line), and eculizumab (dotted line). CFA0305, CFA0307, ​​CFA0366, CFA0501, CFA0538, CFA0599, CFA0666, CFA0672, and CFA0675 are antibodies classified to antigenic determinant C, and eculizumab is the control group of anti-C5 antibodies. [Figure 5A] Figure 5A shows Western speckle analysis of the peptide fragments derived from the MG1-MG2 domains of the GST-tagged fusion (amino acids 33 to 124, 45 to 124, 52 to 124, 33 to 111, 33 to 108, and 45 to 111 at sequence identification number 40), as described in Example 4.4. An anti-GST antibody was used as the antibody for the reaction, and the positions of the C5 fragments (35 to 37 kDa) of the GST fusion are indicated by arrows. [Figure 5B] Figure 5B shows Western speckle analysis of the peptide fragments derived from the MG1-MG2 domains of the GST-tagged fusion (amino acids 33 to 124, 45 to 124, 52 to 124, 33 to 111, 33 to 108, and 45 to 111 at sequence identification number 40), as described in Example 4.4. CFA0305 was used as the antibody for the reaction. [Figure 5C] Figure 5C summarizes the binding reaction of anti-C5 antibodies to the β-chain extended fragments of C5, as described in Example 4.4. Fragments binding to anti-C5 antibodies classified under antigenic determinant C (CFA0305, CFA0307, ​​CFA0366, CFA0501, CFA0538, CFA0599, CFA0666, CFA0672, and CFA0675) are shown in gray, while fragments not binding to them are shown in white. [Figure 6] Figure 6 shows a Western speckle analysis of C5 point mutants with alanine substitutions at E48, D51, and K109 in the β-chain (E48A, D51A, and K109A, respectively), as described in Example 4.5. In the left column, eculizumab (anti-C5 antibody, α-chain conjugate) was used as the antibody for the reaction, and the position of the α-chain of C5 (approximately 113 kDa) is indicated by arrows. In the right column, CFA0305 (classified as antigenic determinant C, β-chain conjugate) was used as the antibody for the reaction, and the position of the β-chain of C5 (approximately 74 kDa) is indicated by an arrow. [Figure 7] Figure 7 presents BIACORE ® Sensing patterns showing the interaction between eculizumab-F760G4 (top bar) or 305LO5 (bottom bar) and the C5 mutant, as described in Example 4.6. Sensing patterns were obtained by injecting C5-wt (thick curve), C5-E48A (short dashed curve), C5-D51A (long dashed curve), and C5-K109A (thin curve) onto the surface of a sensor immobilized with eculizumab-F760G4 or 305LO5, respectively. Eculizumab is the control group of the anti-C5 antibody, and 305LO5 is a humanized antibody of CFA0305 (classified to antigenic determinant C), as described in Example 2.3. [Figure 8] Figure 8 presents BIACORE. ®Sensing patterns, showing the interaction between 305LO5 and the His mutant of C5 to assess pH dependence, as described in Example 4.7. Sensing patterns were obtained by injecting C5-wt (thick curve), C5-H70Y (long dashed curve), C5-H72Y (short dashed curve), C5-H110Y (dotted curve), and C5-H70Y+H110Y (thin curve) onto a sensor surface immobilized with 305LO5, respectively. The antibody / antigen complex was dissociated at pH 7.4, followed by further dissociation at pH 5.8 (arrow indicated) to assess pH-dependent interaction. [Figure 9A] Figure 9A shows the inhibition of complement activation and liposome cell lysis by anti-C5 antibody, as described in Example 5.1. The results showed that CFA0305, CFA0307, ​​CFA0366, CFA0501, CFA0538, CFA0599, CFA0666, CFA0672, and CFA0675 were classified to antigenic determinant C, as described in Example 2.2. [Figure 9B] Figure 9B shows the inhibition of complement-activated liposome lysis by anti-C5 antibody, as described in Example 5.1. The results showed that antibodies CFA0330 and CFA0341 were classified to antigenic determinant B, as described in Example 2.2. [Figure 10A] Figure 10A shows the inhibition of C5a production by anti-C5 antibody, as described in Example 5.2. The concentration of C5a was quantified in the supernatant obtained in the liposome lysis assay as described in Figure 9A. [Figure 10B] Figure 10B shows the inhibition of C5a production by anti-C5 antibody, as described in Example 5.2. The concentration of C5a was quantified in the supernatant obtained in the liposome lysis assay as described in Figure 9B. [Figure 11] Figure 11 shows the hemolytic reaction of complement activation inhibited by anti-C5 antibody, as described in Example 5.3. Complement is activated via the classical pathway. [Figure 12] Figure 12 shows the hemolytic reaction of complement activation inhibited by anti-C5 antibody, as described in Example 5.4. Complement is activated via the alternative pathway. [Figure 13] Figure 13 shows the time course of plasma human C5 concentration after intravenous administration of human C5 alone or human C5 and anti-human C5 antibody in mice assessed for C5 elimination, as described in Example 6.2. CFA0305, CFA0307, ​​CFA0366, CFA0501, CFA0538, CFA0599, CFA0666, CFA0672, and CFA0675 are antibodies classified to antigenic determinant C, and CFA0330 and CFA0341 are antibodies classified to antigenic determinant B, as described in Example 2.2. [Figure 14] Figure 14 shows the time course of plasma anti-human C5 antibody concentrations in mice after intravenous administration of human C5 and anti-human C5 antibodies in mice for evaluating antibody pharmacokinetics, as described in Example 6.3.CFA0305, CFA0307, ​​CFA0366, CFA0501, CFA0538, CFA0599, CFA0666, CFA0672, and CFA0675 are antibodies classifying to antigenic determinant C, and CFA0330 and CFA0341 are antibodies classifying to antigenic determinant B, as described in Example 2.2. [Figure 15] Figure 15 shows the inhibition of complement-activated liposome cytolysis by anti-C5 antibodies, as described in Example 9.1. Results for antibodies 305LO15-SG422, 305LO16-SG422, 305LO18-SG422, 305LO19-SG422, 305LO20-SG422, and 305LO20-SG115 are shown. [Figure 16] Figure 16 shows the inhibition of complement-activated liposome lysis by anti-C5 antibody, as described in Example 9.1. Results for antibodies 305LO15-SG115 and 305LO23-SG429 are shown. [Figure 17] Figure 17 shows the inhibition of complement-activated liposome lysis by anti-C5 antibody, as described in Example 9.1. Results for antibodies 305LO22-SG115, 305LO22-SG422, 305LO23-SG115, and 305LO23-SG422 are shown. [Figure 18] Figure 18 shows the inhibition of C5a production by anti-C5 antibody, as described in Example 9.2. The concentration of C5a is quantified in the supernatant obtained in the liposome lysis assay described in Figure 15. [Figure 19] Figure 19 shows the inhibition of C5a production by anti-C5 antibody, as described in Example 9.2. The concentration of C5a was quantified in the supernatant obtained in the liposome lysis assay as described in Figure 16. [Figure 20] Figure 20 shows the inhibition of complement activity in monkey plasma by anti-C5 antibody, as described in Example 9.3. Anti-C5 antibody was administered to rhesus monkeys (cynomolgus monkeys), and complement activity in monkey plasma was measured in a hemolysis assay. [Figure 21] Figure 21 shows the inhibition of the bioactivity of wild-type C5 (WT) and C5 variants (V145I, R449G, V802I, R885H, R928Q, D966Y, S1310N, and E1437D) by anti-C5 antibody (eculizumab), as described in Example 9.4. [Figure 22] Figure 22 shows the inhibition of the biological activity of wild-type C5 (WT) and C5 variants (V145I, R449G, V802I, R885H, R928Q, D966Y, S1310N, and E1437D) by anti-C5 antibodies (305 variant), as described in Example 9.4. [Figure 23] Figure 23 shows the inhibition of complement-activated liposome cytolysis by anti-C5 antibodies (BNJ441 and 305 variant), as described in Example 9.5.[Figure 24] Figure 24 shows the time course of plasma C5 concentration in rhesus monkeys after intravenous administration of anti-human C5 antibody to assess C5 elimination, as described in Example 10.2. [Figure 25] Figure 25 shows the time course of plasma anti-human C5 antibody concentration in rhesus monkeys after intravenous administration of anti-human C5 antibody to assess pharmacokinetics, as described in Example 10.3. [Figure 26] Figures 26A and 26B show the crystal structure of 305 Fab bound to the human C5 (hC5)-MG1 domain, as described in Example 11.6. Figure 26A shows the asymmetric unit, with MG1 shown as a surface schematic and 305 Fab shown as bands (dark gray: heavy chain, light gray: light chain). Figure 26B shows overlapping molecules 1 and 2 (dark gray: molecule 1, light gray: molecule 2). [Figure 27A] Figure 27A shows the antigenic determinants located in the 305 Fab contact region on the MG1 domain, as described in Example 11.6. Figure 27A shows the epitope mapping of the MG1 amino acid sequence (dark gray: closer than 3.0 Å, light gray: closer than 4.5 Å). [Figure 27B] Figure 27B shows the antigenic determinants located in the 305 Fab contact region on the MG1 domain, as described in Example 11.6. Figure 27B shows the epitope mapping of the crystal structure (dark gray spherical: closer than 3.0 Å, light gray rod-shaped: closer than 4.5 Å). [Figure 28A] Figure 28A shows a close-up view of the interaction between E48, D51, and K109 (rod image) and 305 Fab (surface image), as described in Example 11.7. [Figure 28B] Figure 28B shows the interaction between E48 and its surrounding environment (dark gray dotted lines: hydrogen bonds with Fab, light gray dotted lines: water-modulated hydrogen bonds), as described in Example 11.7. [Figure 28C] Figure 28C shows the interaction between D51 and its surrounding environment (dark gray dotted lines: hydrogen bonds with Fab), as described in Example 11.7. [Figure 28D] Figure 28D shows the interaction between K109 and its surrounding environment (dark gray dotted lines: hydrogen bonds with Fab, light gray dotted lines: salt bridges with H-CDR3_D95), as described in Example 11.7. [Figure 29A] Figure 29A shows a close-up view of the interaction between H70, H72, and H110 (bar image) and 305 Fab (surface image), as described in Example 11.8, in the same orientation as Figure 28A. [Figure 29B] Figure 29B shows the interaction between H70 and its surrounding environment, as described in Example 11.8. This histidine residue is indicated by rod and network images, and hydrogen bonds are indicated by dotted lines. [Figure 29C] Figure 29C shows the interaction between H72 and its surrounding environment, as described in Example 11.8. This histidine residue is indicated by rod and network images, and hydrogen bonds are indicated by dotted lines.[Figure 29D] Figure 29D shows the interaction between H110 and its surrounding environment as described in Example 11.8. This histidine residue is indicated by rod and mesh images. The distance between H110 and H-CDR3_H100c is represented by dotted lines.

Claims

1. An isolated antibody that binds to C5, wherein the antibody comprises (a) an HVR-H1 comprising the amino acid sequence SSYYX1X2, wherein X1 is M or V, and X2 is C or A (Sequence Identification Number: 126); (b) an HVR-H2 comprising the amino acid sequence X1IX2TGSGAX3YX4AX5WX6KG, wherein X1 is C, A, or G, X2 is Y or F, X3 is T, D, or E, X4 is Y, K, or Q, X5 is S, D, or E, and X6 is A or V (Sequence Identification Number: 127); and (c) an HVR-H3 comprising the amino acid sequence DX1GYX2X3PTHAMX4X5, wherein X1 is G or A, X2 is V, Q, or D, X3 is T or Y, X4 is Y or H, and X5 is L or Y. (Sequence Identification Number: 128); (d) HVR-L1, comprising the amino acid sequence X1ASQX2IX3SX4LA, wherein X1 is Q or R, X2 is N, Q or G, X3 is G or S, and X4 is D, K or S (Sequence Identification Number: 129); (e) HVR-L2, comprising the amino acid sequence GASX1X2X3S, wherein X1 is K, E or T, X2 is L or T, and X3 is A, H, E or Q (Sequence Identification Number: 130); and (f) HVR-L3, comprising the amino acid sequence QX1TX2VGSSYGNX3, wherein X1 is S, C, N or T, X2 is F or K, and X3 is A, T or H (Sequence Identification Number: 131).

2. The antibody as claimed in claim 1 further comprises a heavy chain variable domain frame FR1, which includes an amino acid sequence of sequence identification numbers 132-134; an FR2, which includes an amino acid sequence of sequence identification numbers 135-136; an FR3, which includes an amino acid sequence of sequence identification numbers 137-139; and an FR4, which includes an amino acid sequence of sequence identification numbers 140-141.

3. The antibody as claimed in claim 2 further comprises a light chain variable domain frame FR1, which includes an amino acid sequence of sequence identification number 142-143; an FR2, which includes an amino acid sequence of sequence identification number 144-145; an FR3, which includes an amino acid sequence of sequence identification number 146-147; and an FR4, which includes an amino acid sequence of sequence identification number 148.

4. An antibody comprising a VH sequence with sequence identification number 10 and a VL sequence with sequence identification number 20.

5. The antibody described in any one of claims 1 to 4 is a full-length IgG1 or IgG4 antibody.

6. An isolated nucleic acid encoding an antibody as described in any one of claims 1 to 5.

7. A host cell comprising nucleic acids as described in claim 6.

8. A method for manufacturing antibodies, comprising: Culture the host cells as described in claim 7 in order to produce the antibody.

9. A pharmaceutical formulation comprising an antibody as described in any one of claims 1 to 5 and a pharmaceutically acceptable carrier.

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