ANTI-C5 ANTIBODIES AND THEIR USES

Abstract

The present invention provides monoclonal antibodies that bind to complement factor 5 (C5) protein, and methods for using the same. In various embodiments of the invention, the antibodies are fully human antibodies that bind to the C5 protein. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing C5 activity, thereby providing a means for treating or preventing a C5-related disease or disorder in humans. In some embodiments, the invention provides an anti-C5 antibody that has improved pharmacokinetic and pharmacodynamic properties, for example, a half-life of more than 10 days.

Description

This application is being filed on June 13, 2017 as a PCI International Patent Application and claims the benefit of priority to United States provisional application Nos. 62 / 349,705, filed on June 14, 2016; 62 / 405,561, filed October 7, 2016; and 62 / 422,107, filed on November 15, 2016, the disclosures of each document are incorporated by reference in their entirety. FIELD OF THE INVENTION The present invention relates to antibodies and antigen-binding fragments of antibodies that specifically bind complement factor C5, and therapeutic and diagnostic methods for using such antibodies. BACKGROUND OF THE INVENTION The complement system is a group of plasma proteins that, when activated, lead to lysis of target cells and facilitate phagocytosis through opsoniration. Complement is activated through a series of proteolytic steps by three main pathways: the classical pathway, which is not normally activated by immune complexes, the alternative pathway that can be induced by unprotected cell surfaces, and the of mannose-binding lectin. The three pathways of the complement cascade converge on the proteolytic cleavage of the complement component 5 (C5) protein. Cleavage of complement component 5 (C5) results in the production of fragments C5a and C5b, a process that is critical during activation of the complement cascade. C5a can generate pleiotropic physiological responses through binding to its receptors (Monk et al 2007, Br. J. Pharmacol. 152: 42 9448). C5a is a potent pro-inflammatory mediator that induces chemotactic migration, improves cell adhesion, stimulates the oxidative burst and induces the release of several inflammatory mediators such as histamine or cytokines. C5b mediates the formation of the membrane attack complex (MAC, or C5b-9) that leads to cell liase in the late phases of complement-dependent cytotoxicity (CDC). Furthermore, in nucleated cells that are resistant to cytolysis by C5b-9, sublytic amounts of C5b-9 can cause cellular activation resulting in cell proliferation, generation of pro-inflammatory mediators, and production of extracellular matrix. Monoclonal antibodies to C5 are known in the art and have been described, for example, in US Patent Publications Nos. 9206251, 9107861, 9079949, 9051365, 8999340, 8883158, 8241628, 7999081, 7432356, 7361339, 7279158, 6534058, 6355245, 6074642, 20160051673, 20160031975 , 20150158936, 20140056888, 20130022615, 20120308559, and at 7402015198243, 7402 015134 8 94, WO2015120130, EP2563813B1, Ερ2328616 Β1 and EP2061810B1 . Fully human antibodies that specifically bind to the C5 protein with high affinity and have improved pharmacokinetic properties may be important in the prevention and treatment of various 05-associated diseases (e.g., atypical hemolytic uremic syndrome). BRIEF COMPENDIUM OF THE INVENTION The present invention provides antibodies and antigen-binding fragments thereof that specifically bind to complement factor protein (C5). The antibodies of the present invention are useful, among others, for inhibiting or neutralizing the activity of the C5 protein. In certain embodiments, the antibodies are useful for preventing, treating or ameliorating at least one symptom or indication of a C5-associated disease or disorder in a subject. In certain embodiments, the antibodies may be administered prophylactically or therapeutically to a subject who has or is at risk for having a C5-associated disease or disorder. In certain embodiments, the 07 / I ηη / Ρ7Π7 / Β / ν anti-C5 antibodies are fully human antibodies that bind C5 with high affinity and have improved pharmacokinetic (PK) and pharmacodynamic (PD) properties. Such high affinity antibodies with improved PK / PD can be used to provide superior efficacy, along with less frequent dosing in a subject with a C5-associated disease or disorder. Inattention antibodies may be full length (e.g., an IgGl or IgG4 antibody) or may comprise only an antigen-binding portion (e.g., a Fab, F(ab'): or scFv fragment), and may be modified to affect functionality, for example, to increase persistence in the host or to eliminate residual cfctor functions (Rcddy et al., 2000, J. Immunol. 164: 1925-1933). In certain embodiments, the antibodies may be bi-specific. In a first aspect, the present invention provides isolated recombinant monoclonal antibodies or antigen-binding fragments thereof that specifically bind to the C5 protein. In some embodiments, the antibodies are fully human monoclonal antibodies. Exemplary anti-C5 antibodies of the present invention are listed in Tables 1 and 2 herein. Table 1 sets out the amino acid sequence identifiers of the heavy chain variable regions (HCVR), light chain variable regions (LCVR), heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) and complementarity determining regions. light chain (LCDR1, LCDR2, and LCDR3) exemplary anti-C5 antibodies. Table 2 sets forth the nucleic acid sequence identifiers of the HCVR, LCVR, HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the exemplary anti-C5 antibodies. The present invention provides antibodies, or antigen-binding fragments thereof, comprising an HCVR comprising an amino acid sequence selected from any of the HCVR amino acid sequences listed in Table 2, or a substantially similar sequence thereof. having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides antibodies or antigen-binding fragments thereof, comprising an LCVR that comprises an amino acid sequence selected from any of the LCVR amino acid sequences listed in Table 1, or a substantially similar sequence thereof that has at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides antibodies or antigen-binding fragments thereof, comprising a pair of HCVR and LCVR amino acid sequences (HCVR / LCVR) comprising any of the HCVR amino acid sequences listed in Table 1 paired with any of the LCVR amino acid sequences listed in Table 1. According to certain embodiments, the present invention provides antibodies, or antigen-binding fragments thereof, comprising a pair of HCVR / LCVR amino acid sequences contained within the anti-C5 antibodies. exemplars listed in Table 1. In certain embodiments, the HCVR / LCVR amino acid sequence pair is selected from the group consisting of SEQ ID Nos.: 2 / 10, 18 / 26, 34 / 42, 50 / 53, 66 / 74, 82 / 90, 98 / 106, 98 / 114, 122 / 106, 98 / 130, 138 / 106, 146 / 106, 122 / 130, 146 / 114, 146 / 130, 138 / 130, 154 / 162, 170 / 178, 186 / 194, 202 / 210, 218 / 226, 234 / 242, 250 / 258, 266 / 258, 274 / 282, 290 / 298, 306 / 314, 322 / 330 and 338 / 346. In certain embodiments, the HCVR / LCVR sequence pair is selected from one of SEQ ID Nos.: 50 / 58 (e.g., H4H12161P), 98 / 106 (e.g., H4H12166P), 138 / 106 (e.g., H4H12166P5 ) or 202 / 210 (for example, H4H12170P). In certain embodiments, the present invention provides anti-C5 antibodies or antigen binding fragments thereof comprising an HCVR and an LCVR, said HCVR comprising an amino acid sequence listed in Table 1 that has no more than five amino acid substitutions, and said LCVR comprising a sequence of amino acids listed in Table 1 having no more than two amino acid substitutions. For example, the present invention provides anti-C5 antibodies or antigen binding fragments thereof comprising an HCVR and an LCVR, said HCVR comprising an amino acid sequence of SEQ ID NO: 98 having no more than five amino acid substitutions, and said LCVR comprising an amino acid sequence of SEQ ID NO: 106 having no more than two amino acid substitutions. In another embodiment, the present invention provides anti-C5 antibodies or antigen binding fragments thereof comprising an HCVR and an LCVR, said HCVR comprising an amino acid sequence of SEQ ID NO: 98 having at least one amino acid substitution, and said LCVR comprising an amino acid sequence of SEQ ID NO: 106 having an amino acid substitution. The present invention also provides antibodies, or antigen-binding fragments thereof, comprising a CDR1 heavy chain (HCDR1) comprising an amino acid sequence selected from any of the HCDR1 amino acid sequences listed in Table 1 or a substantially similar sequence of the themselves having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides antibodies, or antigen-binding fragments thereof, comprising a CDR2 heavy chain (HCDR2) comprising an amino acid sequence selected from any of the HCDR2 amino acid sequences listed in Table 1 or a substantially similar sequence of the themselves having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides antibodies, or antigen-binding fragments thereof, comprising a CDR3 heavy chain (HCDR3) comprising an amino acid sequence selected from any of the HCDR3 amino acid sequences listed in Table 1 or a substantially similar sequence of the themselves having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides antibodies, or antigen-binding fragments thereof, comprising a CDR1 light chain (LCDR1) comprising an amino acid sequence selected from any of the LCDR1 amino acid sequences listed in Table 1 or a substantially similar sequence of the same having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides antibodies, or antigen-binding fragments thereof, comprising a CDR2 light chain (LCDR2) comprising an amino acid sequence selected from any of the LCDR2 amino acid sequences listed in Table 1 or a substantially similar sequence of the themselves having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides antibodies, or antigen-binding fragments thereof, comprising a CDR3 light chain (LCDR3) comprising an amino acid sequence selected from any of the LCDR3 amino acid sequences listed in Table 1 or a substantially similar sequence of the themselves having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides antibodies, or antigen-binding fragments thereof, comprising an HCDR3 amino acid sequence pair and an LCDR3 (HCDR3 / LCDR3) comprising any of the HCDR3 amino acid sequences listed in Table 1 paired with any of the LCDR3 amino acid sequences listed in Table 1. According to certain embodiments, the present invention provides antibodies, or antigen-binding fragments thereof, comprising an HCDR3 / LCDR3 amino acid sequence pair contained within any of the anti-antibodies. C5 exemplars listed in Table 1. In certain embodiments, the HCDR3 / LCDR3 amino acid sequence pair is selected from the group consisting of SEQ ID Nos.: 56 / 64 (e.g., H4H12161P), 104 / 112 (e.g., H4H12166P), 144 / 112 (e.g. H4H12166P5) and 208 / 216 (e.g. H4H12170P). The present invention also provides antibodies, or antigen-binding fragments thereof, comprising an HCVR and an LCVR, said HCVR comprising HCDR1 comprising an amino acid sequence different from the amino acid sequence listed in Table 1 for 1 amino acid, HCDR2 comprising an amino acid sequence different from the amino acid sequence listed in Table 1 per 1 amino acid, and HCDR3 comprising an amino acid sequence different from the amino acid sequence listed in Table 1 per 1 amino acid. In certain embodiments, the present invention provides antibodies, or antigen-binding fragments thereof, comprising an HCVR and an LCVR, said LCVR comprising LCDR1 comprising an amino acid sequence different from the amino acid sequence listed in Table 1 for 1 amino acid, LCDR2 comprising an amino acid sequence different from the amino acid sequence listed in Table 1 per 1 amino acid, and LCDR3 comprising an amino acid sequence different from the amino acid sequence listed in Table 1 per 1 amino acid. For example, the present invention provides C-5 antibodies or antigen-binding fragments thereof, comprising an HCVR and an LCVR, said HCVR comprising HCDR1 comprising an amino acid sequence of SEQ ID NO: 100 c; amino acid different from SEQ ID NO: 100 per 1 amino acid, HCDR2 comprising an amino acid sequence of SEQ ID NO: 102 or an amino acid sequence different from SEQ ID NO: 102 per 1 amino acid, and HCDR3 comprising an amino acid sequence of SEQ ID NO: 104 or an amino acid sequence different from SEQ ID M°: 104 for 1 amino acid. In another exemplary embodiment, the present invention provides antibodies, or autogen-binding fragments thereof, comprising an HCVR and an LCVR, said LCVR comprising LCDR1 comprising an amino acid sequence of SEQ ID NO: 108 or a different amino acid sequence of SEQ ID NO: 108 for 1 amino acid, LCDR2 comprising an amino acid sequence of SEQ ID NO: 110 or a different amino acid sequence of SEQ ID NO: 110 for 1 amino acid, and LCDR3 comprising an amino acid sequence 07 / I ηη / Ρ7Π7 / Β / ν of SEQ ID NO: 112 or an amino acid sequence different from SEQ ID NO: 112 for 1 amino acid. The present invention provides antibodies, or antigen-binding fragments thereof, comprising a heavy chain comprising an amino acid sequence of SEQ ID NO: 353 or a substantially similar sequence thereof having at least 80%, at least 85% , at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereof. The present invention also provides antibodies, or antigen-binding fragments thereof, comprising a light chain comprising an amino acid sequence of SEQ ID NO: 354 or a substantially similar sequence thereof having at least 80%, at least 85 %, at least 90%, at least 95%, at least 98% or at least 99% sequence identity thereof. In certain embodiments, the present invention provides antibodies, or antigen-binding fragments thereof, comprising a heavy chain comprising an amino acid sequence of SEQ ID 4o: 353 or a substantially similar sequence thereof having at least 80%, or at least 90% sequence identity; and a light chain comprising the amino acid sequence of SEQ ID NO: 354, or a substantially similar sequence having at least 80% 07 / I ηη / Ρ7Π7 / Β / ν or at least 90% sequence identity. The present invention also provides antibodies, or antigen-binding fragments thereof, comprising a set of six CRDs, (i.e., HCDR1-HCDR2-HCDR3-LCDR1LCDR2-LCDR3) contained within any of the exemplary anti-C5 antibodies. listed in Table 1. In certain embodiments, the amino acid sequence set HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 is selected from the group consisting of SEQ ID NOs: 52-54-5660-62-64 (for for example, H4H12161P), 100-102-104-108-110-112 (for example, H4H12166P), 140-142-144-108-110-112 (for example, H4H12166P5), and 204-206-208-212-214 -216 (for example H4H12170P). In a related embodiment, the present invention provides antibodies, or antigen-binding fragments thereof, comprising a set of six CRDs, (i.e., HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 contained within a sequence pair of HCVR / LCVR amino acids as defined by any of the exemplary anti-C5 antibodies listed in Table 1. For example, the present invention includes antibodies, antigen binding fragments thereof, comprising the amino acid sequence set HCDR1-HCDR2 -HCDR3-LCDR1-LCDR2-LCDR3 contained within an HCVR / LCVR amino acid sequence pair selected from the group consisting of SEQ ID Nos.: 50 / 58 (e.g., H4H12161P), 98 / 106 (e.g., H4H12166P ), 138 / 106 (e.g., H4H12166P5) or 202 / 210 (e.g., H4H12170P). Methods and techniques for identifying CDRs within the HCVR and LCVR amino acid sequences are well known in the art and can be used to identify CDRs within the specified HCVR / LCVR amino acid sequences disclosed herein. Exemplary conventions that can be used to identify CDR boundaries include, for example, the Kabat definition, the Chotnia definition, and the AbM definition. Broadly speaking, the Kabat definition is based on sequence variability, the Chothia definition is based on the location of structural loop regions, and the AbM definition is a compromise between the Kabat and Chothia approaches. See, for example, Kabat Sequences of Proteins of Immunological Interest!, National Institutes of Health, Bethesda, Md. (1991); AlLacihani et al., J. Mol. Biol. 273:927-948 (1997); and Martin et al. , Proc. Ah you. Academic SciISA 86:9268-9272 (1989). Public databases are also available to identify the CDR sequences within an antibody. In certain embodiments, the present invention includes an antibody or antigen-binding fragment thereof that specifically binds to C5, where the antibody or Q7J I ηη / Ρ7Π7 / Β / ν antigen-binding fragment comprises three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) and three chain CDRs (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR), where the HCVR comprises: (i) the amino acid sequence of SEQ ID NO: 98, (ii) an amino acid sequence that has at least 90% identity with SEQ ID NO: 98, (iii) an amino acid sequence that has at least 95% identity with SEQ ID NO: 98; or (iv) the amino acid sequence of SEQ ID NO: 98 having no more than 5 amino acid substitutions; and the LCVR comprises: (i) the amino acid sequence of SEQ ID NO: 106, (11) an amino acid sequence that has at least 90% identity with SEQ ID NO: 106, (iii) a amino acid sequence that has at least 95% identity with SEQ ID NO: 106; or (iv) the amino acid sequence of SEQ ID NO: 106 having no more than 5 amino acid substitutions. The present invention includes anti-C5 antibodies that have a modified glycosylation pattern. In some embodiments, modification to remove unwanted glycosylation sites may be useful, or an antibody lacking a fucose residue present on the oligosaccharide chain, for example, to increase antibody-dependent cellular cytotoxicity (ADCC) function ( see Shield et al., (2002) JBC 277-26733). In other applications, galactosylation modification can be made in order to modify complement dependent cytotoxicity (CDC). In certain embodiments, the present invention provides antibodies or antigen-binding fragments thereof that exhibit pH-dependent binding to C5. For example, the present invention includes antibodies and antigen-binding fragments thereof that bind C5 with greater affinity at a neutral pH than at an acidic pH (i.e., reduced binding at acidic pH). In certain embodiments, the present invention provides antibodies or antigen-binding fragments thereof that exhibit improved pharmacokinetic and pharmacodynamic properties, for example the present invention provides anti-C5 antibodies that have an extended serum half-life. In certain embodiments, the anti-C5 antibodies of the present invention have a serum concentration of more than 10 pg / mL until day 40 in C5-humanized mice. In certain embodiments, the anti-C5 antibodies of the present invention block CP and AP hemolysis until day 35 after administration to mice. 07 / I ηη / Ρ7Π7 / Β / ν humanized with C5. The present invention also provides antibodies and antigen-binding fragments thereof that compete for specific binding to C5 with an antibody or antigen-binding fragment thereof comprising the CDRs of an HCVR and the CDRs of an LCVR, wherein the HCVR and LCVR each have an amino acid sequence selected from the HCVR and LCVR sequences listed in Table 1. The present invention also provides antibodies and antigen-binding fragments thereof that cross-compete for binding to C5 with a reference antibody or antigen-binding fragment thereof comprising the CDR of an HCVR and the CDR of an LCVR. , where the HCVR and LCVR each have an amino acid sequence selected from the HCVR and LCVR sequences listed in Table 1. The present invention also provides antibodies and antigen-binding fragments thereof that bind to the same epitope as a reference antibody or antigen-binding fragment thereof comprising the CDRs of an HCVR and the CDRs of an LCVR, where the HCVR and LCVR each have an amino acid sequence selected from the HCVR and LCVR sequences listed in Table 1. In certain embodiments, the present invention provides antibodies and antigen binding fragments thereof that bind to the same epitope as an antibody of reference or antigen binding fragment comprising the CDRs of an HCVR and the CDRs of an LCVR, where the HCVR / LCVR sequence pair has SEQ ID N0: s 98 / 106. The present invention also includes anti-C5 antibodies and antigen-binding fragments thereof that bind to one or more amino acid residues comprised in the alpha chain and / or beta chain of C5. In certain embodiments, the present invention provides antibodies and antigen-binding fragments thereof that bind to one or more amino acids in the alpha chain of C5 and one or more amino acids in the beta chain of C5. In certain embodiments, the present invention provides antibodies and antigen binding fragments that bind to one or more amino acids in the alpha and beta chains of C5, where the antibodies do not bind to the anaphylatoxin domain of C5a. In certain embodiments, the present invention provides anti-C5 antibodies that interact with one or more amino acids contained within the C5 stem (SEQ ID NO: 359). In certain embodiments, the present invention provides anti-C5 antibodies that interact with one or more amino acids contained within human C5 (SEQ ID NO: 359), where the antibodies do not bind to the C5a anaphylatoxin domain of C5. Embodiments, the present invention provides anti-C5 antibodies and antigen-binding fragments thereof that interact with an amino acid sequence selected from the group consisting of (a) amino acids 591 to 599 of SEQ IN NO: 359; (b) amino acids 593 to 599 of SEQ ID NO: 359; (c) amino acids 775 to 787 of SEQ ID NO: 359; (d) amino acids 775 to 794 of SEQ ID NO: 359; and (e) amino acids 779 to 787 of SEQ ID NO: 359. In certain embodiments, the present invention provides anti-C5 antibodies and antigen binding fragments thereof that interact with one or more amino acids contained within SEQ ID N No. 359, for example, the present invention provides anti-C5 antibodies and antigen-binding fragments thereof that interact with at least 5 amino acids, at least 10 amino acids, or at least 15 amino acids contained within SEQ ID NO: 361 In certain embodiments, the present invention provides anti-C5 antibodies and antigen binding fragments thereof that interact with one or more amino acids contained within SEQ ID NO: 359, for example, the present invention provides anti-C5 antibodies. and antigen-binding fragments thereof that interact with at least 5 amino acids contained within SEQ ID NO: 360. In certain embodiments, the present invention provides anti-C5 antibodies and antigen-binding fragments thereof that interact with at least 5 amino acids contained within SEQ ID NO: 360 and 361. In certain embodiments, the present invention provides anti-C5 antibodies and antigen binding fragments thereof that interact with the amino acid sequence of SEQ ID NO: 360 (corresponding to amino acids 591 to 599 of SEO ID NO: 359) and with the amino acid sequence of SEQ ID NO: 361 (corresponding to amino acids 775 to 7 94 of SEQ ID NO: 359). In some embodiments, the antibody or antigen-binding fragment thereof may specifically bind to C5 in an agonist manner, i.e. may enhance or stimulate the binding and / or activity of C5; In other embodiments, the antibody may specifically bind to C5 in an antagonistic manner, that is, it may block binding and / or activity to C5. The present invention also provides isolated antibodies and antigen-binding fragments thereof that block the binding of C5 to C5 convertase. In some embodiments, the antibody or antigen-binding fragment thereof that blocks binding of C5 to C5 convertase may bind to the same epitope on C5 as the C5 convertase or may bind to a different epitope on C5 as the convertase. of C5. In some embodiments, the present invention provides antibodies or antigen-binding fragments thereof that block the binding of C5 to monkey C5 convertase. In certain embodiments, the antibodies or antigen-binding fragments of the present invention are biospecific comprising a first binding specificity to a first C5 protein epitope and a second binding specificity to a second C5 protein epitope, where the first and Second epitopes are distinct and do not overlap. In certain embodiments, the antibodies and antigen-binding fragments of the present invention bind to C5 with an IC50 of less than 0.5 nM. In certain embodiments, the antibodies comprise an HCVR comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 290, 306, 322 and 338. In certain embodiments, the antibodies comprise an LCVR comprising an amino acid sequence selected from the group consisting of SEQ ID Nos.: 298, 314, 330 and 346. In certain embodiments, the present invention provides an isolated antibody or antigen-binding fragment thereof that has one or more of the following characteristics: (a) it is a fully human monoclonal antibody; (b) binds to human C5 with a dissociation constant (Kd) of less than 0.9 nM at 25°C, as measured in a surface plasmon resonance assay; (c) binds to human C5 with a Kd of less than 0.3 nM at 37 °C, as measured in a surface plasmon resonance assay; (d) binds to monkey C5 with a Kd of less than 65 nM, as measured in a surface plasmon resonance assay; (e) binds to the human C5 variant R885H (SEQ ID NO: 356) with a Kd of less than 0.5 nM, as measured in a surface plasmon resonance assay; (f) binds to the human C5 variant R885C (SEQ ID NO: 357) with a Kd of less than 0.5 nM, as measured in a surface plasmon resonance assay; (g) blocks classical pathway (CP) hemolysis mediated by human C5 by more than 95% and with IC50 less than 6 nM, as measured in a CP hemolysis assay; (h) blocks human C5-mediated alternative pathway (AP) hemolysis by more than 70% and with IC50 less than 165 nM, as measured in an AP hemolysis assay; (i) inhibits C5-mediated CP hemolysis of the African green monkey with IC50 less than 185 nM, as measured in a CP hemolysis assay; (j) inhibits C5-mediated AP hemolysis of the African green monkey with IC50 less than 235 nM, as measured in an AP hemolysis assay; (k) inhibits C5-mediated CP hemolysis of the cynomolgus monkey with IC50 less than 145 nM, as measured in a CP hemolysis assay; and (1) inhibits C5-mediated AP hemolysis of the cynomolgus monkey with IC50 less than 30 07 / I ηη / Ρ7Π7 / Β / ν nM, as measured in an AP hemolysis assay. In certain embodiments, the present invention provides an isolated recombinant monoclonal anti-C5 antibody or antigen-binding fragment thereof that has one or more of the following characteristics: (a) comprises a set of six CDRs comprising the amino acid sequences of SEQ ID NO: 100-102-104-108-110112; (b) binds to human C5 with a dissociation constant (Kd) of less than 0.2 nM at 25°C, as measured in a surface plasmon resonance assay; (c) binds to human C5 with a Kd of less than 0.3 nM at 37 °C, as measured in a surface plasmon resonance assay; (d) binds to a human C5 variant (R885H) with a Kd of less than 0.4 nM at 37°C, as measured in a surface plasmon resonance assay; (e) inhibits classical pathway (CP)-mediated hemolysis of human serum with an IC50 of less than 3 nM; (f) inhibits alternative pathway (AP) mediated hemolysis of human serum with an IC50 of less than 27 nM; (g) inhibits CP-mediated hemolysis of monkey serum with an IC50 of less than 21 nM; (h) inhibits AP-mediated hemolysis of monkey serum with an IC50 less than 10 nM; (i) has a serum half-life (tb) of more than 10 days in C5-humanized mice; (j) has a serum concentration of more than 10 gg / ml until day 40 after being administered to C5-humanized mice; (k) blocks CP-mediated hemolysis until day 50 in C5-humanized mice; and (1) binds to one or more amino acids comprised in the alpha chain and / or the beta chain of SEQ W NO: 359, where the antibody does not bind to the C5a anaphylatoxin domain of C5. In a second aspect, the present invention provides nucleic acid molecules encoding anti-C5 antibodies or portions thereof. For example, the present invention provides nucleic acid molecules that encode any HCVR amino acid sequence listed in Table 1; In certain embodiments, the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCVR nucleic acid sequences listed in Table 2, or a sequence substantially similar thereto having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides nucleic acid molecules encoding any of the LCVR amino acid sequences listed in Table 1; In certain embodiments, the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCVR nucleic acid sequences listed in Table 2 or a substantially similar sequence that is at least 90%, Q7J I ηη / Ρ7Π7 / Β / ν at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides nucleic acid molecules encoding any of the HCDR1 amino acid sequences listed in Table 1; In certain embodiments, the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCDR1 nucleic acid sequences listed in Table 2 or a sequence substantially similar thereto having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides nucleic acid molecules encoding any of the HCDR2 amino acid sequences listed in Table 1; In certain embodiments, the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCDR2 nucleic acid sequences listed in Table 2 or a sequence substantially similar thereto having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides nucleic acid molecules encoding any of the HCDR3 amino acid sequences listed in Table 1; In certain embodiments, the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCDR3 nucleic acid sequences listed in Table 2 or a sequence substantially similar thereto having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides nucleic acid molecules encoding any of the LCDR1 amino acid sequences listed in Table 1; In certain embodiments, the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCDR1 nucleic acid sequences listed in Table 2 or a sequence substantially similar thereto having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides nucleic acid molecules encoding any of the LCDR2 amino acid sequences listed in Table 1; In certain embodiments, the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCDR2 nucleic acid sequences listed in Table 2 or a sequence substantially similar thereto having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides nucleic acid molecules encoding any of the LCDR3 amino acid sequences listed in Table 1; In certain embodiments, the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCDR3 nucleic acid sequences listed in Table 2 or a sequence substantially similar thereto having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The present invention also provides nucleic acid molecules encoding an HCVR, where the HCVR comprises a set of three CDRs (i.e., HCDR1-HCDR2-HCDR3), where the amino acid sequence set HCDR1-HCDR2-HCDR3 is as defined any of the exemplary anti-C5 antibodies listed in Table 1. The present invention also provides nucleic acid molecules encoding an LCVR, where the LCVR comprises a set of three CDRs (i.e., LCDR1-LCDR2-LCDR3), where the amino acid sequence set LCDR1-LCDR2-LCDR3 is as defined any of the exemplary anti-C5 antibodies listed in Table 1. The present invention also provides nucleic acid molecules encoding both an HCVR and an LCVR, wherein the HCVR comprises an amino acid sequence of either 07 / I ηη / Ρ7Π7 / Β / ν of the HCVR amino acid sequences listed in Table 1 and where LCVR comprises an amino acid sequence of any of the LCVR amino acid sequences listed in Table 1. In certain embodiments, the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCVR nucleic acid sequences listed in Table 2, or a substantially similar sequence thereof having at least 95%, at least 98% or at least 99% sequence identity, and a polynucleotide sequence selected from any of the LCVR nucleic acid sequences listed in Table 1, or a substantially similar sequence having at least 95%, at least 98% or at least 99% sequence identity. In certain embodiments according to this aspect of the irn / cntion, the nucleic acid molecule encodes an HCVR and LCVR, where the HCVR and LCVR are derivatives of the same anti-C5 antibody listed in Table 1. In a related aspect, the present invention provides recombinant expression vectors capable of expressing a polypeptide comprising a heavy or light chain variable region of an anti-C5 antibody. For example, the present invention includes recombinant expression vectors comprising any of the nucleic acid molecules mentioned above, that is, nucleic acid molecules encoding any HCVR sequence, LCVR and / or CDR as set forth in Table 2. Also included within the scope of the present invention are the host cells into which said vectors have been introduced, as well as methods for producing the antibodies or portions thereof by culturing the host cells. under conditions that allow the production of the antibodies or antibody fragments, and recover the antibodies and antibody fragments so produced. In a third aspect, the invention provides a pharmaceutical composition comprising a therapeutically effective amount of at least one recombinant monoclonal antibody or antigen-binding fragment thereof that specifically binds to C5 and a pharmaceutically acceptable carrier. In a related aspect, the invention characterizes a composition that is a combination of an anti-C5 antibody and a second therapeutic agent. In one embodiment, the second therapeutic agent is any agent that is advantageously combined with an anti-C5 antibody. Exemplary agents that may be advantageously combined with an anti-C5 antibody include, without limitation, other agents that bind and / or inhibit the activity of C5 (including other antibodies or antigen-binding fragments thereof, etc.) and / or agents that do not bind directly to C5 but nevertheless treat or improve at least one symptom or indication of a C5-associated disease or disorder. Additional combination therapies or coformulations involving the anti-C5 antibodies of the present invention are disclosed herein. In a fourth aspect, the invention provides therapeutic methods for treating a C5-associated disease or disorder in a subject using an anti-C5 antibody or antigen-binding portion of an antibody of the invention, wherein the therapeutic methods comprise administering an amount therapeutically effective of a pharmaceutical composition comprising an antibody or antigen-binding fragment of an antibody of the invention to a subject in need thereof. The disorder treated is any disease or condition that is ameliorated, inhibited or prevented by inhibiting C5 activity. In certain embodiments, the invention provides methods for preventing, treating or improving at least one symptom of atypical hemolytic uremic syndrome (aHUS), the method comprising administering a therapeutically effective amount of an anti-C5 antibody or antigen-binding fragment of the invention. to a subject who needs it. In some embodiments, the present invention provides methods of improving or reducing the severity of at least one symptom or indication of paroxysmal nocturnal hemoglobinuria (PNH) in a subject by administering an anti-C5 antibody of the invention. In some embodiments, the antibody or antigen-binding fragment thereof may be administered prophylactically or therapeutically to a subject who has or is at risk for having a C-5-associated disease or disorder. In certain embodiments, the antibody or antigen-binding fragment of the invention is administered in combination with a second therapeutic agent to the subject in need thereof. The second therapeutic agent may be selected from the group consisting of an anti-inflammatory drug (such as corticosteroids, and non-spheroidal anti-inflammatory drugs), an antibody other than C5 protein, a dietary supplement such as anti-oxidants and any other drug or therapy known in the art. In certain embodiments, the second therapeutic agent may be an agent that helps counteract or reduce any possible side effect associated with an antibody or antigen binding fragment thereof of the invention, should that side effect occur. The antibody or fragment thereof can be administered subcutaneously, intravenously, intradermally, intraperitoneally, orally or intramuscularly. The antibody or fragment thereof can be administered at a dose of about 0.1 mg / kg body weight to about 100 mg / kg body weight of the 07 / I ηη / Ρ7Π7 / Β / ν subject. In certain embodiments, an antibody of the present invention may be administered in one or more doses ranging from 50 mg to 600 mg. The present invention also includes the use of an anti-C5 antibody or antigen binding fragment of the invention in the manufacture of a medicament for the treatment of a disease or disorder that would benefit from blocking C5 binding and / or or activity. Other embodiments will be evident from the following detailed description. BRIEF DESCRIPTION OF THE FIGURES Figure 1 shows the inhibition of C5a levels by the anti-C5 antibody H4H12166P in a dose-dependent manner, as determined by ELISA (described in Example 9 of this document). Figure 2 shows the total serum concentration vs time after a single intravenous injection of 15 mg / kg of H4H12166P, H4H12161P or Comparator 2 to male cynomolgus monkeys (described in Example 10 of this document). Concentration time profiles were plotted at the first dose following the limit of quantitation (BLQ) result, if applicable, which was imputed as LLOQ / 2. Each data point represents the mean (+SD) (n = 4 animals / group); concentrations considered affected by ADA were excluded from 1 animal in the H4H12166P group and 1 animal in the H4H12161P group from Day 36 and Day 2 9, respectively. LLOQ = Lower limit of quantification. Figures 3A-3B show the percentage of hemolysis as a function of time in red blood cells ex vivo (A) Classic Route and (B) Alternative Route after a single intravenous injection of H4H12166P, H4H12161P or Comparator 2 for male cynomolgus monkeys. % hemolysis, calculated as a ratio of experimental lysis vs. maximum lysis with % background lysis subtracted from both values, is related to the amount of C5 inhibited by the particular anti-C5 antibody present in the serum at a time. given. Each data point represents the mean (+SD). Figure 4 shows the total serum concentration vs time profiles of anti-C5 antibodies selected in mice humanized for C5 (described in Example 11 of this document). Humanized C5 mice were administered a single subcutaneous dose of 15 mg / kg of H4H12166P, Comparator 1 or Comparator 2. Each data point represents the mean ± s.e.m. (n = 4-5 each). Antibody concentrations in sera were monitored 1, 10, 20, 30, and 40 days after injection using an interleaved ELISA. Figure 5 shows the percentage of hemolysis vs. time in a hemolysis assay by classical ex vivo complement pathway of anti-C5 antibodies selected in mice humanized for C5. Humanized C5 mice were administered a single subcutaneous dose of 15 mg / kg of H4H12166P, Comparator 1 or Comparator 2. Each data point represents the mean ± s.e.m. (n = 4-5 each). The percentage of hemolysis in serum was monitored before administration, 10, 20, 30, 40 and 50 days after injection. % hemolysis, calculated as a ratio of experimental lysis vs maximum lysis with % background lysis subtracted from both values, is related to the amount of C5 inhibited by the particular anti-C5 antibody present in the serum at a given time. . Figure 6 shows the total serum concentration vs. time profiles of selected anti-C5 antibodies in mice humanized for C5 (described in Example 11 of this document). Mice were administered a single subcutaneous dose of 15 mg / kg of H4H12166P, H4H12161P, Comparator 1, or IgG4p isotype control. Each data point represents the mean + s.e.m. (n = 5 each). Antibody levels in the sera were monitored 6 hours, 1, 2, 3, 4, 7, 10, 14, 21, 30, 45 and 59 days after injection. 07 / I ηη / Ρ7Π7 / Β / ν using an interleaved ELISA. Figure 7 is a graph showing optical coherence tomography (OCT) scores in mice treated with isotype control or with the anti-C5 antibody M1M17628N at 10 mg / kg or 50 mg / kg (described in Example 14 of this document). pCO.OOOl, two-way ANOVA treatment with anti-C5 antibody at 50 mg / kg vs no treatment or isotype control treatment. Figures 8A-8B show the inhibition of hemolysis by the classical route by the anti-C5 antibody M1M17628N in the absence of C3 (A); and in the presence of 80 pg / mi of human C3 (B) (described in Example 14 of this document). Figure 9 shows sectioning of cell groups in humanized C5 mice treated with isotype control or with anti-human C5 antibody H4H12170P at 10 mg / kg or 50 mg / kg (described in Example 15 of this document). n = 8-12 eyes for each group. Figure 10 is a graph showing OCT scores in humanized C5 mice treated with isotype control or with the anti-human C5 antibody H4H12170P at 10 mg / kg or 50 mg / kg (described in Example 15 of this document). n = 8-12 eyes for each group Figure 11 is a graph showing OCT scores in humanized C5 mice treated with isotype control, anti-human C5 antibody H4H12166P at 3 mg / kg or 10 07 / I ηη / Ρ7Π7 / Β / ν mg / kg, or Comparator 2 at 10 mg / kg. o = 6-12 eyes for each group (described in Example 15 herein). Figure 12 shows cell cluster counting in humanized C5 mice treated with isotype control, C5 anti-human antibody H4H12166P at 3 mg / kg or 10 mg / kg, or Comparator 2 at 10 mg / kg. n = 6-12 eyes for each group (described in Example 15 herein). Figure 13 is a survival curve of NZBWF1 mice treated with isotype control or with anti-C5 antibodies M1M17628N or M1M17627N (described in Example 17 of this document). Figures 14A-14B show the levels of (A) urinary albumin and (B) urinary albumin normalized to urinary creatinine in NZBWF1 mice treated with isotype control or with anti-C5 antibodies M1M17628N or M1M17627N (described in Example 17 of this document). . Figure 15 shows blood urea nitrogen levels in NZBWF1 mice treated with isotype control or with anti-C5 antibodies M1M17628N or M1M17627N (described in Example 17 of this document). Figure 16 is a graph showing the inhibition of antibody-dependent cytotoxicity of astrocytes by the anti-C5 antibodies H4H12166P, H4H12170P, Comparator 1 and Comparator 2, as described in Example 18. 07 / I ηη / Ρ7Π7 / Β / ν DETAILED DESCRIPTION Before describing the present methods, it should be understood that this invention is not limited to the particular methods and experimental conditions described, as said methods and conditions may vary. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, as the scope of the present invention will be limited only by the appended claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one skilled in the art to which this invention pertains. Although any methods and materials similar or equivalent to those described herein may be used in the practice or testing of the present invention, preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference in their entirety. Definitions The term C5 also called complement component 5 or complement factor 5 refers to the serum protein of the complement cascade. The C5 protein 07 / I ηη / Ρ7Π7 / Β / ν is a protein of 1676 amino acids that comprises two chains, alpha and beta. The protein represents the convergence point for three complement activation pathways: classical pathway, alternative pathway, and mannose-binding lectin pathway. The amino acid sequence of the full-length C5 protein is exemplified by the amino acid sequence provided in GenBank under accession number NP_001726.2 (SEQ ID NO: 355). The term C5 includes the recombinant C5 protein or a fragment thereof. The term also encompasses the C5 protein or a fragment thereof coupled to, for example, histidine tag, mouse or human Fe, or a signal sequence such as ROR1 . For example, the term includes sequences exemplified by the sequence shown in SEQ ID NO: 356 or 357, which comprises a histidine tag at the C terminus, coupled to amino acid residues 19-1676 of the full-length C5 protein. . The term also includes protein variants comprising a C-terminal histidine tag coupled to amino acid residues 19-1676 of the full-length C5 protein with an R885H change or an R885C change. The term antibody as used herein is intended to refer to immunoglobulin molecules composed of four polypeptide chains, two heavy (H) chains and two light (L) chains interconnected by disulfide bonds (i.e., antibody molecules). complete), as well as multimers thereof (for example IgM) or antigen-binding fragments thereof. Each heavy chain is composed of a heavy chain variable region (HCVR or Vh) and a heavy chain constant region (composed of ChI, Ch2 and Ch3 domains). Each light chain is composed of a light chain variable region (LCVR or Vl) and a light chain constant region (Cl). The Vh and Vl regions can be further subdivided into regions of hypervariability, called complementarity determining regions (CDR), interspersed with more conserved regions, called framework regions (FR). Each Vh and Vl is composed of two CDRs and four FRs, arranged from the amino end to the carboxy end in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. In certain embodiments of the invention, the FRs of the antibody (or antigen-binding fragment thereof) may be identical to human germline sequences, or may be modified naturally or artificially. A consensus amino acid sequence can be defined based on a side-by-side analysis of two or more CDRs. Substitution of one or more CDR residues or omission of one or more CDRs is also possible. Antibodies have been described in the scientific literature in which one or two CDRs can be dispensed with for binding. Padlan et al., (1995 PHASES J. 9: 133-139) analyzed the contact regions between antibodies and their autogens, based on published crystal structures, and concluded that only about one-fifth to one-third of the CDR residues actually they contact the antigen. Padlan also found many antibodies in which one or two CDRs did not have amino acids in contact with the antigen (see also, Vajdos et al., 2002 J. Mol Biol 320:415,428). CDR residues that do not contact the antigen can be identified based on previous studies (e.g. residues H60-H65 in CDRH2 are not often required), from Kabat CDR regions that lie outside the Chotnia CDRs, for example. molecular modeling and / or empirically. If a CDR or residue thereof is omitted, it is generally substituted with an amino acid that occupies the corresponding position in another human antibody sequence or a consensus of such sequences. The positions for substitution within the CDRs and amino acids to substitute can also be selected empirically. Empirical substitutions can be conservative or non-conservative substitutions. The fully human anti-C5 monoclonal antibodies disclosed herein may comprise one or more amino acid substitutions, insertions and / or deletions in the frame and / or CDR regions of the heavy and light chain variable domains compared to the corresponding sequences of the germ line. Such mutations can be easily determined by comparing the amino acid sequences disclosed herein with germline sequences available from, for example, public antibody sequence data sets. The present invention includes antibodies, and antigen-binding fragments thereof, which are derived from any of the amino acid sequences disclosed herein, where one or more amino acids within one or more frameworks and / or CDR regions are mutated to the corresponding residue of the germline sequence from which the antibody is derived, or the corresponding residue of another human germline sequence, or to a conservative amino acid substitution of the corresponding germline residue (such sequence changes are collectively referred to herein as germline mutations). A person of ordinary skill in the art, starting with the heavy and light chain variable region sequences described herein, can easily produce numerous antibodies and antigen-binding fragments comprising one or more individual germline mutations or combinations of the same. In certain embodiments, all CDR frameworks and / or residues within the Vr and / or Vl domains are mutated back to residues found in the original germline sequence from which the antibody is derived. In other embodiments, only certain residues are mutated back to the original germline sequence, for example, only the mutated residues found within the first 8 amino acids of FR1 or within the last 8 amino acids of ER4, or only the residues mutants found within CDR1, CDR2 or CDR3. In other embodiments, one or more of the CDR frameworks and / or residues are mutated to the corresponding residue of a different germline sequence (i.e., a germline sequence that is different from the germline sequence from which the antibody was originally derived). Furthermore, the antibodies of the present invention may contain any combination of two or more germline mutations within the y / c framework; CDR regions, for example, where certain individual residues are mutated to the corresponding residue of a particular germline sequence while other residues that differ from the 07 / I ηη / Ρ7Π7 / Β / ν original germline sequence are maintained or moved to the corresponding residue of a different germline sequence. Once obtained, antibodies and antigen-binding fragments containing one or more germline mutations can be easily tested for one or more desired properties, such as, improved binding specificity, increased binding affinity, agonistic biological properties. or improved antagonists (as the case may be), reduced immunogenicity, etc. Antibodies and antigen-binding fragments obtained in this general manner are encompassed within the present invention. The present invention also includes fully human anti-C5 monoclonal antibodies comprising variants of any of the HCVR, LCVR and / or CDR amino acid sequences described herein that have one or more conservative substitutions. For example, the present invention includes anti-C5 antibodies having HCVR, LCVR and / or CDR amino acid sequences with, for example, 10 or less, 8 or less, 6 or less, 4 or less, etc. conservative amino acid substitutions with respect to any of the HCVR, LCVR and / or CDR amino acid sequences described herein. The term human antibody as used herein 07 / I ηη / Ρ7Π7 / Β / ν document, is intended) to include antibodies that have constant and variable regions derived from human germline immunoglobulin sequences. The human mAbs of the invention may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs. and in particular CDR3. However, the term human antibody, as used herein, is not intended to include mAbs in which CDR sequences derived from the germline of another mammalian species (e.g., mice), have been grafted onto FR sequences. human. The term includes antibodies produced recombinantly in a non-human mammal, or in cells of a non-human mammal. The term is not intended to include antibodies isolated from or generated in a human subject. The term recombinarite as used herein refers to antibodies or antigen-binding fragments of the invention created, expressed, isolated or obtained by technologies or methods known in the art as recombinant DNA technology that includes, for example, splicing. DNA and transgenic expression. The term refers to antibodies expressed in a non-human mammal (including transgenic non-human mammals, for example, transgenic mice), or a cellular expression system (for example, CHO cells) or isolated from a library of recombinant human combinatorial antibodies. The term specifically binds or specifically binds to or the like means that an antibody or antigen-binding fragment thereof forms a complex with an antigen that is relatively stable under physiological conditions. Specific binding can be characterized by an equilibrium dissociation constant of at least about 1 x 10" M or less (for example, a lower Kd denotes tighter binding). Methods for determining whether two molecules bind specifically are well known in the art or include, for example, equilibrium dialysis, surface plasmon resonance, and the like. As described herein, antibodies have been identified by surface plasmon resonance, for example BIACORE™, which specifically binds to C5. Furthermore, multi-specific antibodies that bind to one domain in C5 and one or more additional autogens or a bi-specific that binds to two different regions of C5 are however considered specifically binding antibodies as used in this document. 07 / I ηη / Ρ7Π7 / Β / ν The term high affinity antibody refers to those mAbs that have a binding affinity to C5, expressed as Kd, of at least 10 uM; preferably 10“ M; more preferably 10"i0M, even more preferably 10"111'4, even more preferably 10"1214, measured by surface plasma resonance, for example, BIACORE™ or solution affinity ELISA. By the term rate of decay, Koff or kd means an antibody that dissociates from C5, with a rate constant of 1 x 10"33"2o less, preferably 1 χ 10-4s-1o less, as determined by surface plasmon resonance, for example, BIACORE™. The terms autogen-binding portion of an antibody, antigen-binding fragment of an antibody, and the like, as used herein, include any synthetic or genetically modified polypeptide or glycoprotein of natural origin, obtainable in the wild that specifically binds to an antigen to form a complex. The terms antigen-binding fragment of an antibody, or antibody fragment, as used herein, refer to one or more fragments of an antibody that retain the ability to bind to the C5 protein. In specific embodiments, the antibody or fragments Q7J I ηη / Ρ7Π7 / Β / ν antibody of the invention may be conjugated to a moiety such as a ligand or a therapeutic moiety (immunoconjugate), a second anti-C5 antibody or any other therapeutic moiety useful for treating an associated disease or disorder. to C5. An isolated antibody as used herein refers to an antibody that is substantially free of other antibodies (Abs) that have different antigenic specificities (for example, an isolated antibody that specifically binds to C5, or a fragment thereof, It is substantially free of Abs that specifically bind to antigens other than C5. A blocking antibody or a neutralizing antibody as used herein (or an antibody that neutralizes the activity of C5 or an antagonistic antibody) refers to an antibody whose binding to C5 results in the inhibition of at least one biological activity of C5. . For example, an antibody of the invention can prevent or block complement-mediated hemolysis via the classical pathway or alternative pathway. The term surface plasmon resonance as used herein refers to an optical phenomenon that allows the analysis of biomolecular interactions in real time by detecting alterations in protein concentrations within a biosensor array, e.g. example using the BIACORE™ system (Pharmacia Biosensor AB, Uppsala, Sweden and Piscataway, N.J.). The term Kd as used herein refers to the equilibrium dissociation constant of a particular antibody-antigen interaction. The term epitope refers to an antigenic determinant that interacts with a specific antigen binding site in the variable region of an antibody molecule known as a paratope. A single antigen can have more than one epitope. Therefore, different antibodies can bind to different areas on an antigen and can have different biological effects. The term epitope also refers to a site on an antigen to which B and / or T cells respond. It also refers to a region of an antigen that is bound by an antibody. Epitopes can be defined as structural or functional. Functional epitopes are generally a subset of structural epitopes and have those residues that directly contribute to the affinity of the interaction. Epitopes can also be conformational, that is, composed of nonlinear amino acids. In certain embodiments, the epitopes may include determinants that are groups of surface chemically active molecules such as amino acids, sugar side chains, phosphoryl groups or sulfonyl groups and, in certain embodiments, may have specific three-dimensional structural characteristics and / or charge characteristics. specific. The term cross-competition as used herein means an antibody or antigen-binding fragment thereof that binds to one antigen and inhibits or blocks the binding of another antibody or antigen-binding fragment thereof. The term also includes competition between two antibodies in both orientations, that is, a first antibody binding and blocking the binding of the second antibody and vice versa. In certain embodiments, the first antibody and the second antibody can bind to the same epitope. Alternatively, the first and second antibodies may bind to different or overlapping epitopes such that binding of one inhibits or blocks binding of the second antibody, for example, by spherical hindrance. Cross-competition between antibodies can be measured by methods known in the art, for example, by a real-time label-free biolayer interferometry assay. Cross-competition between two antibodies can be expressed as the binding of the second antibody that is less than the background signal due to self-binding (where the first and second antibodies are the same antibody). Cross-competition between 2 antibodies can be expressed, for example, as the % binding of the second antibody that is less than the background binding of the background (where the first and second antibodies are the same antibody). The term substantially identical or substantially identical, when referring to a nucleic acid or fragment thereof, indicates that, when optimally aligned with the appropriate nucleotide insertions or deletions with another nucleic acid (or its complementary strand), there is a nucleotide sequence identity in at least about 90%, and more preferably at least about 95%, 96%, 97%, 98% or 99% of the nucleotide bases, as measured by the well-known sequence identity algorithm, such as FASTA, BLAST or GAP, as discussed below. A nucleic acid molecule that has substantial identity to a reference nucleic acid molecule may, in certain cases, encode a polypeptide that has the same or substantially similar amino acid sequence to the polypeptide encoded by the reference nucleic acid molecule. As applied to polypeptides, the term substantial similarity or substantially similar means that two peptide sequences, when aligned in such a way 07 / I ηη / Ρ7Π7 / Β / ν optimal, such as by the GAP or BESTFIT programs using predetermined space weights, share at least 90% sequence identity, even more preferably at least 95%, 98% or 99% identity of sequence. Preferably, the residue positions, which are not identical, differ by conservative amino acid substitutions. A conservative amino acid substitution is one in which one amino acid residue is replaced by another amino acid residue that has a side chain (R group) with similar chemical properties (e.g., charge or hydrophobicity). In general, a conservative amino acid substitution will not substantially change the functional properties of a protein. In cases where two or more amino acid sequences differ from each other by conservative substitutions, the percentage or degree of similarity may be adjusted upward to correct for the conservative nature of the substitution. Means for making this adjustment are well known to those skilled in the art. See, for example, Pearson (1 994) Methods Mol. Biol. 24:307-331, which is incorporated herein by reference. Examples of groups of amino acids that have side chains with similar chemical properties include 1) aliphatic side chains: glycine, alanine, valine, leucine and isoleucine; 2) hydroxyl side chains 07 / I ηη / Ρ7Π7 / Β / ν aliphatic: serine and threonine; 3) amine-containing side chains: asparagine and glutamine; 4) aromatic side chains: phenylalanine, tyrosine and tryptophan; 5) basic side chains: lysine, arginine and histidine; 6) acidic side chains: aspartate and glutamate, and 7) sulfur-containing side chains: cysteine ​​and methionine. Preferred conservative amino acid substitution groups are: al ina-1 eucine-i sol eucine, f en i 1 al anine-ti resin, 1 i sinaarginine, alanine-valine, glutamate-aspartate and asparagineglutamine. Alternatively, a conservative replacement is any change that has a positive value in the log likelihood matrix PAM25C) disclosed in Gonnet et al (1992) Science 256: 1443-45, incorporated herein by reference. A moderately conservative replacement is any change that has a non-negative value in the log probability matrix ΡΆΜ250. Sequence similarity for polypeptides is normally measured using sequence analysis software. Protein analysis software matches similar sequences using similarity measures mapped to various substitutions, deletions, and other modifications, including conservative amino acid substitutions. For example, GCG software contains programs such as GAP and BESTFIT that can be used with predetermined parameters to determine sequence homology or sequence identity between closely related polypeptides, such as homologous polypeptides from different species of organisms or between a type protein. wild and a mutein thereof. See, for example, GCG Version 6.1. Polypeptide sequences can also be compared with default or recommended FASTA parameters; a program in GCG Version 6.1. FASTA (e.g. FASTA2 and FASTA3) provides alignments and percentage sequence identity of the regions of best overlap between query and search sequences (Pearson (2000) supra). Another preferred algorithm when comparing a sequence of the invention to a database containing a large number of sequences from different organisms is the BLAST comparison program, especially BLASTP or TBLASTN, using predetermined parameters. See, for example, Altschul et al., (1990) J.Mol. Biol. 215:4 03-4 4 0 and (1997) Nucí ele Acid Res. 25:338 9-34 02, each of which is incorporated herein by reference. The phrase therapeutically effective amount means an amount that produces the desired effect for which it is administered. The exact amount will depend on the purpose of the treatment, and will be verified by a person skilled in the art using known techniques (see, for example, Lloyd (1999) The Art, Science and Technology of Pharmaceutical Compounding). As used herein, the term subject refers to an animal, preferably a mammal, more preferably a human, in need of improvement, prevention and / or treatment of a C5-associated disease or disorder such as atypical hemolytic uremic syndrome ( aHUS) or paroxysmal nocturnal hemoglobinuria (PNH). The term includes human subjects who have or are at risk for such disease or disorder. As used herein, the term treats, treating or treatment refers to the reduction or improvement of the severity of at least one symptom or indication of a C5-associated disease or disorder due to the administration of a therapeutic agent such as an antibody. of the present invention to a subject who needs it. Terms include inhibition of disease progression or worsening of a symptom / indication. The terms also include a positive prognosis of the disease, that is, the subject may be free of the disease or have reduced disease following administration of a therapeutic agent such as an antibody of the present invention. The therapeutic agent may be administered in a therapeutic dose to the subject. The terms prevent, preventing or prevention refer to the inhibition of the manifestation of a C5-associated disease or disorder or any symptoms or indications of said disease or disorder following administration of an antibody of the present invention. Antigen-binding fragments of Antibodies Unless specifically indicated otherwise, the term antibody as used herein is understood to encompass antibody molecules comprising two immunoglobulin heavy chains and two immunoglobulin light chains (i.e., full antibody molecules) as well as antigen binding fragment thereof. The terms antigen-binding portion of an antibody, antigen-binding fragment of an antibody, and the like, as used herein, include any naturally occurring, enzymatically obtainable, synthetic or genetically modified polypeptide or glycoprotein that specifically binds to an antigen to form a complex. The terms antigen-binding fragment of an antibody, or antibody fragment as used herein, refers to one or more fragments of an antibody that retain the ability to specifically bind to the C5 protein. An antibody fragment may include a Lab fragment, an F(ab')2 fragment, an Fv fragment, a dAb fragment, a fragment containing a CDR, or an isolated CDR. In certain embodiments, the term "antigen-binding fragment" refers to a polypeptide fragment of a multispecific antigen-binding molecule. Antigen-binding fragments of an antibody can be derived, for example, from whole antibody molecules using any suitable standard technique such as proteolytic digestion or recombinant genetic engineering techniques involving the manipulation and expression of variable and (optionally) constant domains of antibodies that encode DNA. Such DNA is known and / or is readily available from, for example, commercial sources, DNA libraries (including, for example, phage-antibody libraries), or can be synthesized. DNA can be cut and manipulated chemically or using molecular biology techniques, for example, to arrange one or more variable and / or constant domains in a suitable configuration, or to introduce codons, create cysteine ​​residues, modify, add or delete amino acids. , etc. Non-limiting examples of antigen-binding fragments include: (i) Fab fragments; (i i ) fragments F(ab')z; (iii) Fd fragments; (iv) Fv fragments; (v) single chain Fv (scFv) molecules; (vi) dAb fragments; and (vii) minimal recognition units consisting of amino acid residues that mimic the hypervariable region of an antibody (e.g., an isolated complementary age-determining region (CDR) such as a CDR3 peptide), or an FR3-CDR3 restricted peptide. -FR4. Other designed molecules, such as domain-specific antibodies, single domain antibodies, domain-deleted antibodies, chimeric antibodies, CDR-grafted antibodies, diabodies, triabodies, tetrabodies, minibodies, nanobodies (e.g., monovalent nanobodies, bivalent nanobodies, etc.) , small modular immunopharmaceuticals (SMIPs) and shark IgNAR variable domains, and also encompassed within the term antigen binding fragment as used herein. An antigen-binding fragment of an antibody will typically comprise at least one variable domain. The variable domain may be of any size or amino acid composition and will generally comprise at least one CDR, which is adjacent to or in frame with one or more framework sequences. In antigen binding fragments having a Vn domain associated with a Vl domain, the Vn and Vl domains may be located relative to each other in any suitable arrangement. For example, the variable region may be dimeric and contain Vh-Vh, Vh-Vl Vl-Vl dimers. Alternatively, the antigen-binding fragment of a 07 / I ηη / Ρ7Π7 / Β / ν antibody may contain a monomeric Vh or Vl domain. In certain embodiments, an antigen-binding fragment of an antibody may contain at least one variable domain covalently linked to at least one constant domain. Non-limiting, exemplary configurations of constant and variable domains that may be found within an antigen-binding fragment of an antibody of the present invention include: (i) Vh-ChI; (ii) Vh Ch2 ; (iii) Vh-Ch3; (iv) Vh-ChI-Ch2; (v) Vh-Ch1-Ch2-Ch3; (vi) VH- Ch2 - Ch3; (vii) VH-CL; (viii) VL-CH1; (ix) VLCh2; (x) Vl-Ch3; (xi) Vl-ChI-Ch2; (xii) Vl - ChI - Ch2 Ch3; (xiii) Vl — Ch2 — Ch3; and (xiv) Vl—Cl· In any configuration of variable and constant domains, including any of the exemplary configurations listed above, the variable and constant domains may be directly linked to each other or may be linked by a complete link or joint region or partial. A hinge region may consist of at least 2 (e.g., 5, 10, 15, 20, 40, 60 or more) amino acids, resulting in a flexible or semiflexible bond between an adjacent variable and / or constant domains in a single polypeptide molecule. Furthermore, an antigen-binding fragment of an antibody of the present invention may comprise a homo-dimer or heterodimer (or other multimer). 07 / I ηη / Ρ7Π7 / Β / ν of any of the constant and variable domain configurations listed above in non-covalent association with each other and / or with one or more Vh or Vl monomeric domains (for example, by disulfide bond). As in the case of complete antibody molecules, the antigen-binding fragments can be mono-specific or multi-specific; (e.g. bispecific). A multispecies antigen-binding fragment of an antibody will typically comprise at least two different variable domains, where each variable domain is capable of specifically binding to a separate antigen or to a different epitope on the same antigen. Any multi-specific antibody format, including the exemplary bi-specific antibody formats disclosed herein, can be adapted for use in the context of an antigen-binding fragment of an antibody of the present invention using routinely available techniques. in the technique. Preparation of human antibodies Methods for generating human antibodies in transgenic mice are known in the art. Any such known method can be used in the context of the present invention to make human antibodies that specifically bind to the C5 protein. 07 / I ηη / Ρ7Π7 / Β / ν An immunogen comprising any of the following can be used to generate antibodies to the C5 protein. In certain embodiments, the antibodies of the invention are obtained from mice immunized with a native, full-length C5 protein (see, for example, GenBank accession number NP_001726.2 (SEQ ID NO: 355) or with DNA encoding the protein or fragment thereof. Alternatively, the protein or fragment thereof can be produced using standard and modified biochemical techniques and used as an immunogen. In certain embodiments of the invention, the immunogen is a fragment of the C5 protein that varies from approximately 1 9 - 1676 amino acid residues of SEQ ID NO: 355. In some embodiments, the immunogen may be a recombinant C5 protein or fragment thereof expressed in E. coli or any other eukaryotic or mammalian cell such as Chinese hamster ovary (CHO) cells. Using VELOCIMMUNE® technology (see, for example, US 6,596,541, Regeneren Pharmaceuticals, VELOCIMMUNE® or any other known method for generating monoclonal antibodies, high affinity chimeric antibodies to C5 are initially isolated having a human variable region and a constant region VELOCIMMUNE® technology involves the generation of a transgenic mouse having a genome comprising human heavy chain and light chain variable regions operably linked to the mouse endogenous constant region loci such that the mouse produces an antibody. comprising a human variable region and a mouse constant region in response to antigenic stimulation The DNA encoding the variable regions of the heavy and light chains of the antibody is isolated and operatively linked to the DNA encoding the heavy chain constant regions The DNA is then expressed in a cell capable of expressing the complete human antibody. Generally, a VELOCIMMUNE® mouse is stimulated with the antigen of interest, and lymphatic cells (such as B cells) are recovered from the antibody-expressing mice. Lymphatic cells can be fused with a myeloma cell line to prepare immortal hybridoma cell lines, and said hybridoma cell lines are analyzed and selected to identify hybridoma cell lines that produce antibodies specific for the antigen of interest. DNA encoding the heavy chain and light chain variable regions can be isolated and linked to desirable isotopic constant regions of the heavy chain and light chain. Said antibody protein can be produced in a cell, such as a cell CHO. Alternatively, DNA encoding chimeric antigen-specific antibodies or light and heavy chain variable domains can be isolated directly from antigen-specific lymphocytes. Initially, high affinity chimeric antibodies are isolated having a human variable region and a mouse constant region. As in the experimental section below, antibodies are characterized and selected for desirable characteristics, including affinity, selectivity, epitope, etc. The mouse constant regions are replaced with a desired human constant region to generate the fully human antibody of the invention, for example wild-type or modified IgGl or IgG4. While the selected constant region may vary depending on the specific use, high affinity antigen binding characteristics and target specificity reside in the variable region. 07 / I ηη / Ρ7Π7 / Β / ν The anti-C5 antibodies and antibody fragments of the present invention encompass proteins that have amino acid sequences that vary from those of the described antibodies, but that retain the ability to bind to the C5 protein. Such variant antibodies and antibody fragments comprise one or more additions, deletions, or substitutions of amino acids when compared to the primary sequence, but exhibit biological activity that is essentially equivalent to those of the described antibodies. Likewise, DNA sequences encoding the antibody of the present invention encompass sequences that comprise one or more nucleotide additions, deletions, or substitutions when compared to the disclosed sequence, but that encode an antibody or antibody fragment that is essentially bioequivalent. to an antibody or antibody fragment of the invention. Two antigen-binding proteins, or antibodies, are considered bioequivalent if, for example, they are pharmaceutical equivalents or pharmaceutical alternatives whose rate and extent of absorption do not show a significant difference when supplied at the same molar mass under similar experimental conditions, either in single dose or multiple doses. Some antibodies will be considered equivalent or pharmaceutical alternatives if they are equivalent in the extent of their absorption but not in their absorption rate and yet may be considered bioequivalent because such differences in absorption rate are intentional and reflected in the labeling, they are not essential to achieve effective drug concentrations in the body, for example, chronic use, and 07 / I ηη / Ρ7Π7 / Β / ν are considered medically insignificant for the particular drug product studied. In one embodiment, two antigen-binding proteins are bioequivalent if there are no clinically significant differences in their safety, purity or potency. In one embodiment, two antigen-binding proteins are bioequivalent if a patient can be switched one or more times between the reference product and the biological product without an expected increase in the risk of adverse effects, including a clinically significant change in immunogenicity. or decreased effectiveness, compared to continued therapy without such change. In one embodiment, two antigen-binding proteins are bioequivalent if they both act by a common mechanism or mechanisms of action for the condition or conditions of use, to the extent that such mechanisms are known. Bioequivalence can be demonstrated by in vivo and / or in vitro methods. Bioequivalence measures include, for example, (a) in vivo testing in humans or other mammals, in which the concentration of the antibody or its metabolites is measured in blood, plasma, serum, or other biological fluids as a function of time; (b) an in vitro test that has been correlated with and is reasonably predictive of human in vivo bioavailability data; (c) in vivo testing in humans or other mammals in which the appropriate acute pharmacological effect of the antibody (or its target) is measured as a function of time; and (d) in a well-controlled clinical trial that establishes safety, efficacy, or bioavailability or bioequivalence of an antibody. Bioequivalent variants of the antibodies of the invention can be constructed, for example, by making various residue or sequence substitutions or eliminating terminal or internal residues or sequences not necessary for biological activity. For example, cisterna residues not essential for biological activity can be removed or replaced with other amino acids to prevent the formation of unnecessary or incorrect intramolecular disulfide bridges upon renaturation. In other contexts, bioequivalent antibodies may include antibody variants that comprise amino acid changes, which modify the glycosylation characteristics of the antibodies, for example, mutations that eliminate or remove glycosylation. Anti-C5 Antibodies Comprising Fe Variants According to certain embodiments of the present invention, anti-C5 antibodies are provided that comprise an Fe domain comprising one or more mutations that 07 / I ηη / Ρ7Π7 / Β / ν enhance or decrease the binding of the antibody to the FcRn receptor, for example, at an acidic pH compared to a neutral ρΗ. For example, the present invention includes anti-C5 antibodies comprising a mutation in the Ch2 region or a Cr3 region of the Fe domain, where the mutation increases the affinity of the FcRn domain in an acidic environment, (for example, in an endosome where pH ranges from about 5.5 to about 6.0). Such mutations can cause an increase in the serum half-life of the antibody when administered to an animal. Non-limiting examples of such Fe modifications include, for example, a modification at position 250 (e.g., E or Q); 250 and 428 (e.g. L or F); 252 (e.g. L / Y / FAV or T), 254 (e.g. S or T) and 256 (e.g. S / R / Q / E / D or T); or a modification at position 428 and / or 433 (e.g. H / L / R / S / P / Q or K) and / or 434 (e.g. A, W, H, F or Y [N434A, N434W , N434H, N434F or N434Y]); or a modification in position 250 and / or 428; or a modification at position 307 or 308 (e.g., 308F, V308F) and 434. In one embodiment, the modification comprises a modification 428L (e.g., M428L) and 434S (e.g., N434S); a modification 428L, 2591 (e.g. V259I) and 308F (e.g. V308F); a 433K modification (e.g., H433K) and a 434 modification (e.g., 434Y); a modification of 252, 254 and 256 (for example, 2521', 254T and 256E); a modification of 250Q and 428L (for example, T250Q and M428L); and a 307 and / or 308 modification (e.g., 308F or 308P). In yet another embodiment, the modification comprises a modification 265A (e.g., D265A) and / or a modification 297A (e.g., N297A). For example, the present invention includes anti-C5 antibodies comprising an Fe domain comprising one or more pairs or groups of mutations selected from the group consisting of: 250Q and 248L (for example, T250Q and M248L); 252Y, 07 / I ηη / Ρ7Π7 / Β / ν 254T and 256E (e.g. M252Y, S254T and T256E); 428L and 434S (e.g. M428L and N434S); 2571 and 3111 (e.g. P257I and Q311I); 2571 and 434H (for example, P257I and N434H1; 376V and 4 34H (for example, D376V and N434H); 307 Λ, 380Λ and 434Λ (for example, T307A, E380A and N434A); and 433K and 434F (for example, H433K and N434F).All possible combinations of the above Fe domain mutations and other mutations within the antibody variable domains described herein are contemplated within the scope of the present invention. The present invention also includes anti-C5 antibodies that comprise a chimeric heavy chain constant (Ch) region, where the chimeric Ch region comprises segments derived from the Ch regions of more than one immunoglobulin isotype. For example, the antibodies of the invention may comprise a chimeric Ch region comprising part or all of the Ch2 domain derived from a human IgGl, human IgG2 or human IgG4 molecule, combined with part or all of the Ch3 domain derived from a human IgGl molecule, Human IgG2 or human IgGl. According to certain embodiments, the antibodies of the invention comprise a chimeric Ch region having a chimeric hinge region. For example, a chimeric hinge may comprise a top hinge amino acid sequence (amino acid residues from positions 216 to 227 according to EU numbering) derived from a human IgGl, human IgG2 or human IgG4 hinge region, combined with a lower hinge sequence (amino acid residues from positions 228 to 236 according to EU numbering) derived from the human IgGl, human IgG2 or IgG4 hinge region. According to certain embodiments, the chimeric hinge region comprises amino acid residues derived from the human IgGl, or human IgG4, upper hinge and amino acid residues derived from a human IgG2 lower hinge. An antibody comprising a chimeric Ch region as described herein may, in certain embodiments, exhibit modified Fe effector functions without adversely affecting the therapeutic c pharmacodynamic properties of the antibody. (See, for example, Patent Application Publication 2014 / 0243504, the disclosure of which is incorporated by reference in its entirety. Biological characteristics of Antibodies In general, the antibodies of the present invention function by binding to the C5 protein and preventing its cleavage to C5a and C5b. For example, the present invention includes antibodies and antigen-binding fragments of antibodies that bind to the C5 protein (e.g., at 25°C or 37°C) with a Kd of less than 9 nM as measured by plasmen resonance. surface, for example, using assay format as defined in Example 3 herein. In certain embodiments, the antibodies or antigen binding fragments bind to C5 with a Kd of less than 9 nM, less than about 5 nM, less than about 2 nM, less than about 1 nM, less than about SCO pM, less of 250 pM, less than 100 pM, measured by surface plasmen resonance, for example, using the assay format as defined in Example 3 herein, or a substantially similar assay. The present invention also includes antibodies and antigen-binding fragments thereof that bind to the human C5 protein with a dissociative half-life (td) greater than about 2 minutes as measured by resonance. 07 / I ηη / Ρ7Π7 / Β / ν of surface plasma at 25 ° C, for example using an assay format as defined in Example 4 herein, or a substantially similar assay. In certain embodiments, the antibodies or antigen binding fragments of the present invention bind to the C5 protein with tb greater than about 5 minutes, greater than about 10 minutes, greater than about 30 minutes, greater than about 50 minutes, greater than about 100 minutes, greater than about 150 minutes, greater than about 200 minutes, or greater than about 250 minutes, measured by surface plasmon resonance at 25°C, for example using an assay format as defined in Example 3 herein document (e.g., mAb capture format or antigen capture format) or a substantially similar assay. The present invention also includes antibodies and antigen-binding fragments thereof that bind to the human C5 protein with a dissociative half-life (tb) greater than about 1.5 minutes as measured by surface plasmon resonance at 37°C, e.g. using an assay format as defined in Example 4 herein, or a substantially similar assay. In certain embodiments, the antibodies or antigen-binding fragments of the present invention bind to the C5 protein with a tb greater than Q7J I ηη / Ρ7Π7 / Β / ν approximately 2 minutes, greater than approximately 5 minutes, greater than approximately 10 minutes, greater than approximately 25 minutes, greater than approximately 50 minutes, greater than approximately 100 minutes, greater than approximately 150 minutes, or greater than approximately 200 minutes, measured by surface plasmen resonance at 37°C, for example using an assay format as defined in Example 3 herein (e.g., mAb capture format or antigen capture format) or a substantially similar assay . The present invention also includes antibodies or antigen-binding fragments of antibodies that bind to the monkey C5 protein (e.g. at 25°C or 37°C) with a Kd of less than 120 nM as measured by surface plasmon resonance. , for example using an essay format as defined in Example 3 in that document. In certain embodiments, antibodies or antigen-binding fragments of antibodies that bind to the monkey C5 protein with a KD of less than about 120 nM, less than about 100 nM; less than about 50 nM, less than about 25 nM, less than about 10 nM, less than about 5 nM, less than about 1 nM, less than about 500 pM, less than about 250 pM, measured by surface plasmon resonance, for example using a test format as defined in Example 3 herein or a substantially similar test. The present invention also includes antibodies and antigen-binding fragments of antibodies that bind to human C5 protein modified with the R885H change (exemplified by SEQ ID NO: 356) with a Kd of less than 70 nM measured by plasmon resonance. of surface, for example using a test format as defined in Example 3 in this document. C5 variants have shown a poor response to anti-C5 antibodies previously disclosed in the art (e.g., Nishimura, et al., 2014, New Engl. J. Med. 370:632-639). In certain embodiments, the antibodies or antigen binding fragments bind to modified human C5 with a Kd of less than about 65 nM, less than about 50 nM, less than about 20 nM, less than about 1OnM, less than about 5 nM , less than about 3 nM, or less than 2 nM, measured by surface plasmen resonance, for example using the assay format as defined in Example 3 herein, or a substantially similar assay. The present invention also includes antibodies and antigen-binding fragments of antibodies that bind to human C5 protein modified with the R885C change (exemplified by SEQ ID NO: 357) with a Kd of less than 160 nM measured by plasmon resonance. of surface, for example using a test format as defined in Example 3 in this document. C5 variants have shown a poor response to anti-C5 antibodies previously disclosed in the art (e.g., Nishimura, et al., 2014, New Engl. J. Med. 370:632-639). In certain embodiments, the antibodies or antigen binding fragments bind to modified human C5 with a Kd of less than about 150 nM, less than about 100 nM, less than about 50 nM, less than about 20 nM, less than about 10 nM, less than about 5 nM, or less than 2 nM, measured by surface plasmon resonance, for example using the assay format as defined in Example 3 herein, or a substantially similar assay. The present invention also includes antibodies and antigen-binding fragments of antibodies that inhibit complement-dependent cytotoxicity (CDC) with IC50 of less than 10 nM measured by luminescence assay, for example using the assay format as defined in Example 6 in this document. In certain embodiments, the antibodies or antigen-binding fragments thereof inhibit CDC with IC50 of less than about 5 nM, less than about 3.5 nM, or less than about 2 nM, as measured by B cell luminescence assay, for example using the assay format as defined in Example herein, or a substantially similar assay. The present invention also includes antibodies and antigen-binding fragments that block hemolysis of the classical pathway mediated by human C5 (CE) by more than 94% and with an IC50 ce less than 6 nM, measured by a CP hemolysis assay, for example using the essay format as defined in Example 8 in that document. In certain embodiments, the antibodies or antigen-binding fragments thereof block CP hemolysis with IC50 of less than about 6 nM, less than about 5 nM; monos of about 4 nM, less than about 3 nM, or less than about 2 nM, measured by CP hemolysis assay, for example using the assay format as defined in Example 8 herein, or a substantially similar assay. The present invention also includes antibodies and antigen-binding fragments that block human C5-mediated alternative pathway (AP) hemolysis by more than 70% and with an IC50 of less than 165 nM, measured by an AP hemolysis assay, for example using the essay format as defined in Example 8 in that document. In certain 07 / I ηη / Ρ7Π7 / Β / ν embodiments, the antibodies or antigen-binding fragments thereof block AP hemolysis with IC50 of less than about 160 nM, less than about 150 nM; less than about 100 nM, less than about 50 nM, or less than about 20 nM, measured by AP hemolysis assay, for example using the assay format as defined in Example 8 herein, or a substantially similar assay. The present invention also includes antibodies and antigen-binding fragments that block hemolysis of the classical pathway mediated by African green monkey (CP) C5 by more than 40% and with a ZC50 of less than 185 nM, measured by a CP hemolysis, for example using the assay format as defined in Example 8 in this document. In certain embodiments, the antibodies or antigen-binding fragments thereof block CP hemolysis with IC50 of less than about 180 nM, less than about 150 nM; less than about 100 nM, less than about 75 nM, or less than about 50 nM, measured by CP hemolysis assay, for example using the assay format as defined in Example 8 herein, or a substantially similar assay. The present invention also includes antibodies and antigen-binding fragments that block hemolysis of 07 / I ηη / Ρ7Π7 / Β / ν the alternative pathway mediated by African green monkey (AP) C5 by more than 70% and with an IC50 of less than 235 nM, measured by an AP hemolysis assay, for example using the test format as defined in Example 8 in this document. In certain embodiments, the antibodies or antigen-binding fragments thereof block AP hemolysis with IC50 of less than about 200 nM, less than about 150 nM; less than about 100 nM, less than about 50 nM, or less than about 20 nM, measured by AP hemolysis assay, for example using the assay format as defined in Example 8 herein, or a substantially similar assay. The present invention also includes antibodies and antigen-binding fragments that block more than 90% of classical pathway hemolysis mediated by cynomolgus monkey (CP) C5 by more than 40% and with an IC50 of less than 145 nM. , measured by a CP hemolysis assay, for example using the assay format as defined in Example 8 herein. In certain embodiments, the antibodies or antigen-binding fragments thereof block CP hemolysis with IC50 of less than about 140 nM, less than about 120 nM; less than about 100 nM, less than about 7 5 nM, or less than about 50 nM, measured by CP hemolysis assay, for example using the assay format as defined in Example 8 herein, or a substantially similar assay. The present invention also includes antibodies and antigen-binding fragments that block cynomolgus monkey (AL) C5-mediated alternative pathway hemolysis with an IC50 of less than 30 nM, measured by an AP hemolysis assay, for example using the test format as defined in Example 8 in this document. In certain embodiments, the antibodies or antigen-binding fragments thereof block AP hemolysis with IC50 of less than about 25 nM, less than about 20 nM; less than about 1OnM, less than about 5 nM, or less than about 2 nM, measured by AP hemolysis assay, for example using the assay format as defined in Example 8 herein, or a substantially similar assay. The present invention also includes antibodies and antigen-binding fragments that exhibit improved pharmacokinetic (PK) and pharmacodynamic (PD) properties compared to anti-C5 antibodies in the art. The anti-C5 antibodies of the present invention show less susceptibility to target-mediated clearance upon administration, as shown in Examples 9 and 10 herein. In certain embodiments, the present invention 07 / I ηη / Ρ7Π7 / Β / ν includes anti-C5 antibodies and antigen-binding fragments thereof that show serum concentrations for extended periods, e.g. more than 20 days, more than 25 days, more than 30 days , more than 35 days, more than 40 days, more than 45 days, more than 50 days, more than 55 days, or more than 60 days, as described in Examples 9 and 10. In certain embodiments, the Anti-C5 antibodies of the present invention show an extended serum half-life of more than 10 days, compared to anti-C5 antibodies in the art. In certain embodiments, the present invention provides anti-C5 antibodies and antigen-binding fragments thereof that have high affinity for human C5 (e.g. Kd less than 0.3 r.M) and lower clearance (e.g. extended serum half-life). , improved pharmacodynamic activity over more days than previously known anti-C5 antibodies). Said antibodies of the present invention can be used advantageously with less frequent dosing in a subject with a C-5 associated disease or disorder. In certain embodiments, the present invention provides an isolated recombinant antibody or antigen-binding fragment thereof that specifically binds to the C5 protein, wherein the antibody or fragment thereof 07 / I ηη / Ρ7Π7 / Β / ν exhibits one or more of the following characteristics: (a) is a fully human monoclonal antibody; (b) binds to human C5 with a dissociation constant (Kd) of less than 0.9 nM at 25 °C, measured in a surface plasmon resonance assay; (c) binds to human C5 with a Kd of less than 0.3 nM at 37 °C, measured in a surface plasmon resonance assay; (d) has serum concentration of more than 10 pg / mL until day 70 after administration to cynomolgus monkey; (e) blocks CP and AP hemolysis until day 35 after administration to the cynomolgus monkey, measured in an ex vivo hemolysis assay; (f) has serum half-life of more than 10 days in cynomolgus monkey; (g) has serum concentration of more than 10 pg / mL until day 40 after administration to humanized C-5 mice; (h) blocks CP hemolysis until day 30 after administration to humanized C5 mice, measured in an ex vivo hemolysis assay; and (i) has serum half-life of more than 10 days in humanized C5 mice. In one embodiment, the present invention provides an isolated recombinant antibody or antigen-binding fragment that specifically binds to the C5 protein, wherein the antibody or fragment thereof exhibits one or more of the following characteristics: (a) it is a monoclonal antibody completely human; (b) binds to human C5 with a dissociation constant (Kd) of less than 0.9 nM at 25 °C, 07 / I ηη / Ρ7Π7 / Β / ν measured in a surface plasmen resonance test; (c) binds to human C5 with a Kd of less than 0.3 nM at 37°C, measured in a surface plasmen resonance assay; (d) binds to monkey C5 with a Kd of less than 65 nM, measured in a surface plasmen resonance assay; (e) binds to the human C5 variant R885H (SEQ ID NO: 356) with a Kd of less than 0.5 nM, measured in a surface plasmen resonance assay; (f) binds to the human C5 variant R8 8 5C (SEQ ID NO: 357) with a Kd of less than 0.5 nM, measured in a surface plasmen resonance assay; (g) blocks classical pathway hemolysis mediated by human C5 (CP) by more than 95% and with IC50 of less than 6 nM, measured in a CP hemolysis assay; (h) blocks hemolysis of the alternative pathway mediated by human C5 (AP) by more than 70% and with IC50 of less than 165 nM, measured in an AP hemolysis assay; (i) inhibits African green monkey C5-mediated CP hemolysis with IC50 of less than 185 nM, measured in a CP hemolysis assay; (j) inhibits African green monkey C5-mediated AP hemolysis with IC50 of less than 235 nM, measured in an AP hemolysis assay; (k) inhibits C5-mediated CP hemolysis of monkey cynomolgc with IC50 of less than 145 nM, measured in a CP hemolysis assay; and (1) inhibits monkey cynomolgc C5-mediated CP hemolysis with IC50 of less than 30 nM, measured in an AP hemolysis assay. The antibodies of the present invention may possess one or more of the aforementioned biological characteristics, or any combination thereof. Other biological characteristics of the antibodies of the present invention will be apparent to a person of ordinary skill in the art from a review of the present disclosure including the Working Examples herein. Epitope mapping and related technologies The present invention includes anti-C5 antibodies that interact with one or more amino acids found within one or more regions of the 05 protein molecule including, alpha polypeptide and beta polypeptide. The epitope to which antibodies bind may consist of a single contiguous sequence of 3 or more (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 , 17, 18, 19, 20 or more) amino acids located within any of the aforementioned domains of the C5 protein molecule (for example, a linear epitope in a domain). Alternatively, the epitope may consist of a number of non-contiguous amino acids (or amino acid sequences) located within either or both of the aforementioned domains of the protein molecule (e.g., a conformational epitope). Various techniques known to persons of ordinary skill in the art can be used to determine whether an antibody interacts with one or more amino acids within a polypeptide or protein. Exemplary techniques include, for example, routine cross-blocking assays, such as that described in Antibodies, Harlow and Lane (Coid Spring Harbor Press, Coid Spring Harbor, NY). Other methods include alanine scanning mutational analysis, peptide blot analysis (Reineke (2004) Methods Mol.Biol. 248: 443-63), crystallographic studies of peptide cleavage analysis and NMR analysis. Additionally, methods such as epitope cleavage, epitope extraction and chemical modification of antigens can be used (Tomer (2000) Prot. Sci. 9: 487-496. Another method that can be used to identify amino acids within a polypeptide with which an antibody interacts is hydrogen / deuterium exchange detected by mass spectrometry. Generally speaking, the hydrogen / deuterium exchange method involves deuterium labeling of the protein of interest, followed by binding of the antibody to the labeled protein with deuterium. The protein / antibody complex is then transferred to water and the exchangeable protons within the amino acids that are protected by the antibody complex undergo an exchange of deuterium to hydrogen at a slower rate than the exchangeable protons within of amino acids that are not part of the interface. As a result, amino acids that are part of the protein / antibody interface can retain deuterium and, therefore, exhibit a relatively higher mass compared to amino acids not included in the interface. After antibody dissociation, the target protein is subjected to protease cleavage analysis and mass spectrometry, thereby revealing deuterium-labeled residues that correspond to the specific amino acids with which the antibody interacts. See, for example, Ehring (1999) Analytical Biocnemistry 267: 252-259; Engen and Smith (2001) Anal. Chcm. 73:2 5 6A-2 657U The term epitope refers to a site on an antigen to which B and / or T cells respond. B cell epitopes can be formed from contiguous amino acids or juxtaposed noncontiguous amino acids by tertiary folding of a protein. Epitopes formed from contiguous amino acids are typically retained upon exposure to denaturating solvents, while epitopes formed by tertiary folding are typically lost upon treatment with denatured solvents. An epitope typically includes at least, and more generally, 07 / I ηη / Ρ7Π7 / Β / ν minus 5 or 8-10 amino acids in a unique spatial conformation. Modification-Assisted Profiling (MAP), also known as Antigen Structure-Based Antibody Profiling (ASAP), is a method that categorizes large quantities of monoclonal antibodies (mAbs) directed against the same antigen according to profile similarities. binding of each antibody to chemically or enzymatically modified antigen surfaces (see US 2004 / 0101920, specifically incorporated herein by reference in its entirety). Each category may reflect a unique epitope either distinctively different from or partially overlapping with the epitope represented by another category. This technology allows rapid filtering of genetically identical antibodies, so that characterization can be focused on genetically distinct antibodies. When applied to hybridoma selection, MAP can facilitate the identification of rare hybridoma clones that produce mAbs that have desired characteristics. MAP can be used to classify antibodies of the invention into groups of antibodies that bind to different epitopes. In certain embodiments, anti-C5 antibodies or antigen-binding fragments thereof bind to an epitope within any one or more of the regions exemplified in the C5 protein, either naturally occurring, as exemplified in SEQ ID N °: 355, or produced recombinantly or a fragment thereof. In some embodiments, the antibodies of the invention bind to a region comprising one or more amino acids selected from the group consisting of amino acid residues 19-1676 of the human C5 protein. In certain embodiments, the antibodies of the invention interact with at least one amino acid sequence selected from the group consisting of amino acid residues ranging from about position 19 to about position 750; or amino acid residues ranging from approximately position 751 to approximately position 1767 of SEQ ID NO: 355. In certain embodiments, the present invention includes anti-C5 antibodies and antigen-binding fragments thereof that interact with one or more epitopes found within the alpha and / or beta chain of C5 (SEQ ID NO: 359). Epitopes may consist of one or more contiguous sequences of 3 or more (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more) amino acids located within the alpha chain and / or beta chain of C5. Alternatively, the epitope may consist of a number of non-contiguous amino acids (or amino acid sequences) located within C5. As shown in Example 11 herein, the C5 epitope with which the exemplary antibody of the invention H4H12166P interacts is defined by: (i) the amino acid sequence NMATGMDSW (SEQ ID NO: 360) which corresponds to the amino acids 591 to 599 included in the beta chain of SEQ ID NO: 359; and (ü) the amino acid sequence WEVHLVPRRKQLQFALPDSL (SEQ ID V: 361), which corresponds to amino acids 775 to 7 94 included in the alpha chain of SEQ ID NO: 359. Consequently, the present invention includes anti-C5 antibodies that interact with one or more amino acids contained within the region consisting of (i) the amino acid sequence NMATGMDSW (SEQ ID NO: 360), which corresponds to amino acids 591 to 599 of SEQ ID NO: 359; and (ü) the amino acid sequence WEVHLVPRRKQLQFALPDSL (SEQ ID NO: 361), which corresponds to amino acids 775 to 794 of SEQ ID NO: 359. The present invention includes anti-C5 antibodies that bind to the same epitope, or a portion of the epitope, as any of the specific exemplary antibodies listed in Table 1. Likewise, the present invention also includes anti-C5 antibodies that compete to bind to the C5 protein or a fragment thereof with any of the specific exemplary antibodies listed in Table 1. For example, the present invention includes anti-C5 antibodies that cross-compete for binding to the C5 protein with one or more antibodies listed in Table 1. One can easily determine whether an antibody binds to the same epitope or competes for binding with a reference anti-C5 antibody using routine methods known in the art. For example, to determine whether a test antibody binds to the same epitope as a reference anti-C5 antibody of the invention, the reference antibody is allowed to bind to the C5 protein or peptide under saturating conditions. Next, the ability of a test antibody to bind to the C5 protein molecule is evaluated. If the test antibody is able to bind to C5 after saturation binding with the reference anti-C5 antibody, it can be concluded that the test antibody binds to a different epitope than the reference anti-C5 antibody. On the other hand, if the test antibody is not able to bind to the C5 protein after saturating binding with the reference anti-C5 antibody, then the test antibody may bind to the same epitope as the epitope bound by the reference anti-C5 antibody of the invention. To determine whether an antibody competes for binding with a reference anti-C5 antibody, the binding methodology described above is carried out in two orientations: In a first orientation, the reference antibody can bind to the C5 protein under conditions of saturation followed by evaluation of the binding of the test antibody to the C5 molecule. In a second orientation, the test antibody can bind to a C5 molecule under saturating conditions followed by evaluation of the binding of the reference antibody to the C5 molecule. If, in both orientations, only the first antibody (saturation) is able to bind to the C5 molecule, then it is concluded that the test antibody and the reference antibody compete to bind to C5. As one skilled in the art will appreciate, an antibody that competes for binding with a reference antibody may not necessarily bind to the identical epitope as the reference antibody, but may spherically block binding of the reference antibody by binding to an overlapping or adjacent epitope. . Two antibodies bind to the same or overlapping epitope if each competitively inhibits (blocks) the binding of the other to the antigen. That is, a 1, 5, 10, 20, or 100-fold excess of one antibody inhibits binding of the other by at least 50%, but preferably 75%, 90%, or even 99%, as measured in a binding assay. competitive (see, for example, Jungnans et al, Cancer Res. 1990 50: 1495-1502). Alternatively, two antibodies have the same epitope if essentially all amino acid mutations in the antigen that reduce or eliminate binding of one antibody reduce or eliminate binding of the other. Two antibodies have overlapping epitopes if some amino acid mutations that reduce or eliminate the binding of one antibody reduce or eliminate the binding of the other. Additional routine experimentation (e.g., peptide mutation and binding analysis) can then be performed to confirm whether the observed lack of binding of the test antibody is actually due to binding to the same epitope as the reference antibody. or whether spherical lock (or other phenomenon) is responsible for the observed nonunion. Experiments of this type can be carried out using ELISA, RIA, surface plasma resonance, flow cytometry or any other quantitative assay; or qualitative antibody binding available in the art. Immunoconjugates The invention encompasses an anti-human C5 monoclonal antibody conjugated to a therapeutic moiety (immunoconjugate), for treating a C5-associated disease or disorder (e.g., atypical hemolytic uremic syndrome). As used in this document, the term 07 / I ηη / Ρ7Π7 / Β / ν immunoconjugate refers to an antibody that is chemically or biologically linked to a radioactive agent, a cytokine, an interferon, a target or reporter moiety, an enzyme, a peptide or protein or a therapeutic agent. The antibody may be linked to the radioactive agent, cytokine, interferon, target or reporter moiety, enzyme, peptide or therapeutic agent at any location along the molecule, as long as it is capable of binding to its target. Examples of immunoconjugates include antibody drug conjugates and antibodytoxin fusion proteins. In one embodiment, the agent may be a second antibody other than the C5 protein. The type of therapeutic moiety that can be conjugated to the anti-C5 antibody will take into account the condition to be treated and the desired therapeutic effect to be achieved. Examples of agents suitable for forming immunoconjugates are known in the art; see, for example, document WO 05 / 103081. Multi-specific antibodies The antibodies of the present invention can be mono-specific, bi-specific or multi-specific. Multi-specific antibodies may be specific for different epitopes of a target polypeptide or may contain antigen-binding domains specific for more than one. 07 / I ηη / Ρ7Π7 / Β / ν a ρο1iρtarget peptide. See, for example, Tutt et al., 1991, J. Immunol. 147:60-69; Kufer et al., 2004, Trends Biotechnol. 22:238-244. Any of the multispecific antigen binding molecules of the invention, or variants thereof, can be constructed using standard molecular biological techniques (e.g., recombinant DNA and protein expression technology), as will be known to one skilled in the art. technique. In some embodiments, C5-specific antibodies are generated in a bi-specific format (a bispecific) in which variable regions that bind different domains of the C5 protein are linked together to confer a dual domain specificity within a single binding molecule. Appropriately designed bi-specifics can enhance the inhibitory efficacy of the C5 protein by increasing both specificity and binding avidity. Variable regions with specificity for individual domains (e.g., segments of the Nterminal domain) or that can bind to different regions within a domain, are paired into a structural scaffold that allows each region to simultaneously bind to separate epitopes, or to different regions within a domain. In an example for a bi heavy chain variable region Q7J I ηη / Ρ7Π7 / Β / ν specific (Vh) from a binder with specificity for one domain are recombined with light chain variable regions (Vl) from a series of binders with specificity for a second domain to identify partners non-cognates that can be paired with an original Vh without interrupting the original specificity for that Vh. In this way, a single Vl segment (e.g., VlI) can be combined with two different Vh domains (e.g., VhI and Vh2) to generate a bi-specific compound of two binding arms (VhI-VlI and Vh2-Vl2). ). The use of a single Vl segment reduces the complexity of the system and therefore simplifies and increases the efficiency in the cloning, expression, and purification processes used to generate the bispecific (See, for example, USSN13 / 022759 and US2010 / 0331527). Alternatively, antibodies that bind more than one domain and a second target, such as, but not limited to, for example, a different second anti-C5 antibody, can be prepared in a bi-specific format using techniques described herein. document, or other techniques known to those skilled in the art. Antibody variable regions that bind to different regions can be linked together with variable regions that bind to relevant sites on, for example, the extracellular domain of C5, to confer antibody specificity. 07 / I ηη / Ρ7Π7 / Β / ν dual antigen within a single binding molecule. Properly designed bispecifics of this nature serve double duty. Variable regions with specificity for the extracellular domain are combined with a variable region with specificity outside the extracellular domain and are paired into a structural scaffold that allows each variable region to bind to separate antigens. An exemplary bi-specific antibody format that can be used in the context of the present invention involves the use of a first immunoglobulin Ch3 (Ig) domain and a second Ig Ch3 domain, where the first and second Ig Ch3 domains differ. one from another by at least one amino acid, and where at least one amino acid difference reduces the binding of the bi-specific antibody to Protein A compared to a bi-specific antibody lacking the amino acid difference. In one embodiment, the first Ig Ch3 domain binds protein A and the second Ig Ch3 domain contains a mutation that reduces or abolishes protein A binding, such as an H95R modification (by IMGT exon numbering; H435R by EU numbering). The second Ch3 may also include a Y96F modification (for IMGT; Y436F for EU). Additional modifications that can be found within the second Ch3 include: D16E L18M, N44S, Κ52Ν, V57M and V82I (by IMGT; D356E, L358M, N384S, K392N, V397M, and V422I by EU) in the case of IgGl antibodies; N44S, K52N and V82I (IMGT; N384S, K392N and ¥4221 per EU) in the case of IgG2 antibodies; and Q15R, N4 4S, K52N, V57M, R69K, E7 9Q and V82I (by IMGT; Q355R, N384S, K392N, V397M, R4O9K, E419Q and V422I by EU) in the case of IgG4 antibodies. Variations in the bispecific antibody format described above are contemplated within the scope of the present invention. Other exemplary bi-specific formats that may be used in the context of the present invention include, without limitation, for example, bi-specific formats based on scFv or diabody, IgG-scFv fusions, variable dual domain (DYD)-Ig, Quadroma, knobs in the hole, common light chain (e.g. common light chain with knobs in the hole, etc.), CrossMab, CrossFab, (SEED)body, leucine zipper, Duobody, IgGl / IgG2, Dual Action Fab (DAF)- IgG and Mab2 bi-specific formats (see for example, Klein et al., 2012, mAbs 4:6, 1-11, and references cited therein, for a review of previous formats). Bispecific antibodies can also be constructed using peptide / nucleic acid conjugation, for example, where unnatural amino acids with orthogonal chemical reactivity are used to generate site-specific oligonucleotide antibody95 conjugates that then self-assemble into multimeric complexes with composition, valence and defined geometry. (See, for example, Kazane et al, J. Am. Chem. Soc. [Epub: December 4, 2012]). Therapeutic Administration and Formulations The invention provides therapeutic compositions comprising the anti-C5 antibodies or antigen-binding fragments thereof of the present invention. Therapeutic compositions according to the invention will be administered with suitable carriers, excipients, and other agents that are incorporated into the formulations to provide improved transfer, administration and tolerance and the like. A multitude of suitable formulations can be found in the formulary known to pharmaceutical chemists: Remington's Pharmaceutical Sciences, Mack Publishing Company, Baston, PA. These formulations include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, lipids (cationic or anionic) containing vesicles (such as LIPOFECTIN™), DNA conjugates, anhydrous absorption pastes, oil-in-water emulsions and water in oil, carbowax emulsions (polyethylene glycols of various molecular weights), semi-solid gels and semi-solid mixtures containing carbowax. See also Powell et al. Compendium of □7 / 1 nn / C7n7 / B / v excipients for parenteral formulations PDA (1998) J Pharm Sel Technol 52: 238-311. The dose of antibody may vary depending on the age and size of the subject to be administered, target disease, conditions, route of administration, and the like. When an antibody of the present invention is used to treat a disease or disorder in an adult patient, or to prevent said disease, it is advantageous to administer the antibody of the present invention usually in a single dose of about 0.1 to about 00 mg / kg of body weight, more preferably about 5 to about 80, about 10 to about 70, or about 20 to about 50 mg / kg body weight. Depending on the severity of the condition, the frequency and duration of treatment may be adjusted. In certain embodiments, the antibody or antigen-binding fragment thereof of the invention may be administered as an initial dose of at least about 0.1 mg to about 800 mg, about 1 to about 600 mg, about 5 to about 500 mg, or about 10 to approximately 400 mg. In certain embodiments, the initial dose may be followed by the administration of a second or a plurality of subsequent doses of the antibody or antigen-binding fragment thereof in an amount that may be approximately the same or less than the initial dose, where the Subsequent doses are separated by at least 1 day to 3 days; at least a week; at least 2 weeks; at least 3 weeks; at least 4 weeks; at least 5 weeks; at least 6 weeks; at least 7 weeks; at least 8 weeks; at least 9 weeks; at least 10 weeks, at least 11 weeks, at least 12 weeks or at least 14 weeks. Various delivery systems are known and can be used to administer the pharmaceutical composition of the invention, for example, encapsulation in liposomes, microparticles, microcapsules, recombinant cells capable of expressing the mutant viruses, receptor-mediated endocytosis (see, for example, Wu ct al., (1987) J. Bio. Chcm. 262: 4429-4432). Methods of introduction include but are not limited to intradermal, transdermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural and oral routes. The composition may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (for example, oral mucosa, rectal and intestinal mucosa, etc.) and may be administered together with other biologically active agents. Administration can be systemic or local. The pharmaceutical composition may also be administered in a vesicle, in particular a liposome (see, for example, Langer 81990) Science 249: 1527-1533). The use of nanoparticles to deliver the antibodies of the present invention is also contemplated herein. Nanoparticles conjugated with antibodies can be used for both therapeutic and diagnostic applications. Antibody-conjugated nanoparticles and methods of preparation and use are described in detail in Arruebo, 14., et al., 2009 (Ant ibody-conjugated nanoparticles for biomedical applications) in J. Nanomat. Volume 2009, Article ID 439389, 24 pages, doi: 10.1155 / 2009 / 439389), incorporated herein by reference. Nanoparticles can be developed and conjugated to antibodies contained in pharmaceutical compositions to target cells. Nanoparticles for drug delivery have also been described in, for example, US 8257740 or US 8246995, each of which is incorporated herein in its entirety. In certain situations, the pharmaceutical composition can be administered in a controlled release system. In one embodiment, a pump may be used. In another embodiment, polymeric materials can be used. In yet another embodiment, a controlled release system can be placed in proximity to the target composition, thus requiring only a fraction of the systemic dose. Injectable preparations may include dosage forms for intravenous, subcutaneous, intracutaneous, intracranial, intraperitoneal and intramuscular injections, drip infusions, etc. These injectable preparations can be prepared by publicly known methods. For example, injectable preparations may be prepared by, for example, dissolving, suspending or emulsifying the antibody or its salt described above in a sterile aqueous medium or an oily medium conventionally used for injections. As an aqueous medium for injections, there are, for example, physiological saline, an isotonic solution containing glucose and other auxiliary agents, etc., which can be used in combination with an appropriate solubilizing agent such as an alcohol (for example, ethanol), a polyalcohol (e.g., propylene glycol, polyethylene glycol), a nonionic surfactant [e.g., polysorbate 80, HCO-50 (polyoxyethylene powder (50 mol) of hydrogenated castor oil)], etc. As an oily medium, for example, sesame oil, soybean oil, etc. are used, which can be used in combination with a solubilizing agent, such as benzoate. 07 / I ηη / Ρ7Π7 / Β / ν 100 benzyl, benzyl alcohol, etc. The injection thus prepared is preferably filled into a suitable ampoule. A pharmaceutical composition of the present invention can be administered subcutaneously or intravenously with a standard needle and syringe. Furthermore, with respect to subcutaneous administration, a pen delivery device has applications in the administration of a pharmaceutical composition of the present invention. Said pen delivery device may be reusable or disposable. A reusable pen delivery device generally uses a replaceable cartridge containing a pharmaceutical composition. Once all of the pharmaceutical composition within the cartridge has been dispensed, and the cartridge is empty, the empty cartridge can be easily discarded and replaced with a new cartridge containing the pharmaceutical composition. The pen delivery device can then be reused. In a disposable pen delivery device, there is no replaceable cartridge. Rather, the disposable pen delivery device comes prefilled with the pharmaceutical composition contained in a reservoir within the device. Once the reservoir is emptied of the pharmaceutical composition, the entire device is discarded. 101 Numerous reusable pen and auto-injector delivery devices have applications in the subcutaneous administration of a pharmaceutical composition of the present invention. Examples include, but are certainly not limited to AUTOPEN™ (Owen Mumford, Inc., Woodstock, United Kingdom), DISETRONIC™ pen (Disetronic Medical Systems, Burghdorf, Switzerland), HUMALOG MIX 75 / 25™ pen, HUMALOG™ pen, HUMALIN 70 / 30™ pen (Eli Lilly and Co . , Indianapolis, IN), NOVOPEN™ I, II and III (Novo Nordisk, Copenhagen, Denmark), NOVOPEN JUNIOR™ (Novo Nordisk, Copenhagen, Denmark), BD™ pen ( Becton Dickinson, Franklin Lakes, NJ), OPTIPEN™, OPTIPEN PRO™, OPTIPEN STARLET™ and OPTICLIK™ (Sanofi-Aventis, Frankfurt, Germany), to name just a few. Examples of disposable pen delivery devices that have applications in the subcutaneous administration of a pharmaceutical composition of the present invention include, but are certainly not limited to, the SOLOSTAR™ pen (Sanofi-Aventis), FLEXPEN™ (Novo Nordisk) and KWIKPEN. ™ (Eli Lilly), SURECLICK™ autoinjector (Amgen, Thousand Oaks, CA), PENLET™ (Haselmeier, Stuttgart, Germany), EPIPEN (Dey, LP), and HUMIRA™ Pen (Abbott Labs, Abbott Park, IL), to name only some. Advantageously, the pharmaceutical compositions for oral and parenteral use described above are prepared in 102 dosage forms in a unit dosage suitable to fit a dosage of the active ingredients. Such dosage forms in a unit dose include, for example, tablets, pills, capsules, injections (blisters), suppositories, etc. The amount of the antibody contained is generally about 5 to about 500 mg per dosage form in a unit dose; especially in the injection form, it is preferred that the antibody is contained in about 5 to about 300 mg and in about 10 to about 300 mg for the other dosage forms. Therapeutic Uses of Antibodies The antibodies of the present invention are useful for the treatment and / or prevention of a disease or disorder or condition associated with C5 and / or for improving at least one symptom associated with said disease, disorder or condition. In certain embodiments, an antibody or antigen-binding fragment thereof of the invention may be administered in a therapeutic dose to a patient with a disease or disorder or condition associated with C5. In certain embodiments, the antibodies of the present invention are useful for treating or preventing a symptom or indication of atypical hemolytic uremic syndrome (aHUS). Symptoms and indications of aHUS include, but are not 07 / I ηη / Ρ7Π7 / Β / ν 103 limited to, platelet activation, hemolysis, systemic thrombotic microangiopathy (blood clot formation in small blood vessels throughout the body) that can cause stroke, heart attack, kidney failure or death, end-stage kidney disease, damage permanent kidney disease, abdominal pain, confusion, edema, fatigue, nausea / vomiting, diarrhea, and microangiopathic anemia. In certain embodiments, the antibodies of the present invention are useful for treating or preventing a symptom or indication of paroxysmal nocturnal hemoglobinuria (PNH). Symptoms and indications of PNH include, but are not limited to, destruction of red blood cells, thrombosis (including deep vein thrombosis, pulmonary embolism), intravascular hemolytic anemia, red discoloration of urine, symptoms of anemia such as tiredness, difficulty breathing, and palpitations, abdominal pain and difficulty swallowing. In certain embodiments, the antibodies of the present invention are useful for treating or preventing at least one symptom or indication of a C5-associated disease or disorder selected from the group consisting of neurological disorders, renal disorders, multiple sclerosis, stroke, Guillain-Barre, injury 104 traumatic brain injury, Parkinson's disease, disorders of inappropriate or unwanted complement activation, hemodialysis complications, hyperacute allograft rejection, xenograft rejection, interleukin-2-induced toxicity during IL-2 therapy, inflammatory disorders, inflammation of autoimmune diseases, Crohn's disease, adult respiratory distress syndrome, thermal injuries including burns or frostbite, post-ischemic reperfusion conditions, myocardial infarction, capillary leak syndrome, obesity, diabetes, Alzheimer's disease, schizophrenia, epilepsy , atherosclerosis, vasculitis, bullous pemphigoid, C3 glomerulopathy, proliferative glomerulonephritis of the membrane, balloon angioplasty, post-pump syndrome in cardiopulmonary bypass or renal bypass, hemodialysis, renal ischemia, mesenteric artery reperfusion after aortic reconstruction, infectious disease or sepsis , immune complex disorders and autoimmune diseases, diabetic nephropathy, Alport syndrome, progressive renal failure, proteinuric kidney diseases, renal ischemia-reperfusion injury, lupus nephritis, glomerulopathy, rheumatoid arthritis, systemic lupus erythematosus (SLE), SLE nephritis, nephritis proliferative, hemolytic anemia, neuromyelitis optica, kidney transplant, deficiency 105 hereditary CD59, psoriasis and myasthenia gravis. In certain other embodiments, the antibodies of the present invention are useful for treating or preventing at least one symptom or indication of a C5-associated disease or disorder selected from the group consisting of lung disease and disorders such as dyspnea, hemoptysis, ARDS, asthma, chronic obstructive pulmonary disease (COPD), emphysema, pulmonary embolisms and infarctions, pneumonia, fibrogenic dust diseases, injuries due to inert dusts and minerals (for example, silicon, coal dust, beryllium and asbestos), pulmonary fibrosis, dust diseases organic, chemical injury (due to irritating gases and chemicals, e.g. chlorine, phosgene, sulfur dioxide, hydrogen sulfide, nitrogen dioxide, ammonia and hydrochloric acid), smoke injury, thermal injury (e.g. burn, frostbite), asthma, allergy, bronchoconstriction, hypersensitivity pneumonitis, parasitic diseases, Goodpasture syndrome, pulmonary vasculitis, hereditary angioedema and inflammation associated with immune complexes. In certain embodiments, the antibodies of the invention are useful for treating subjects suffering from an ocular disease such as age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy, ocular angiogenesis (ocular neovascularization). 1 nn / cznz / B / Y 106 affects the ceroid, corneal or retinal tissue), geographic atrophy (GA), uveitis and neuromyelitis optica. The antibodies of the present invention can be used to treat or improve at least one symptom or indication of dry AMD or wet AMD. In some embodiments, the antibodies of the invention are useful for preventing or slowing vision loss. In one embodiment, the antibodies of the present invention are useful for reducing drusen in the eye of a subject with dry AMD. In one embodiment, the antibodies of the present invention are useful for preventing or reducing / slowing vision loss in a subject with AMD. One or more of the antibodies of the present invention may be administered to alleviate or prevent or lessen the severity of one or more of the symptoms or conditions / indications of the ocular disease or disorder. Antibodies can be used to improve or reduce the severity of at least one symptom including, but not limited to, loss of vision, distortion of vision, difficulty adjusting to low light levels, distorted central vision, increased cloudiness in central / general vision, presence of drusen (small accumulations of extracellular material that accumulate in the retina), pigmentary changes, distorted vision in the form of metamorphosis, 107 where a grid of straight lines appears wavy and parts of the grid may appear white, exudative changes (ocular hemorrhages, hard exudates, sub-retinal / sub-RPE / intra-retinal fluid), slow recovery of visual function after exposure to bright light (photostress test), geographic and incipient atrophy, sharply decreased visual acuity (two levels or more), e.g., 20 / 20 to 20 / 80, preferential perimetric changes of hyperactivity (for wet AMD) , blurred vision, gradual loss of central vision (for those with non-exudative macular degeneration, rapid onset of vision loss (often caused by leaking and bleeding from abnormal blood vessels) in subjects with exudative macular degeneration, central cseotomas ( shadows or missing areas of vision), colors distinguishing problems, especially dark from light and dark, loss of contrast sensitivity, straight lines appear curved on an Amsler grid. It is also contemplated herein to use one or more antibodies of the present invention prophylactically for subjects at risk of developing macular degeneration such as subjects over 50 years of age, subjects with a family history of macular degeneration, smokers, and subjects with 07 / I ηη / Ρ7Π7 / Β / ν 108 obesity, high cholesterol, cardiovascular disease or unhealthy diet. In a further embodiment of the invention the present antibodies are used for the preparation of a pharmaceutical composition or medicament for treating patients suffering from a disease or disorder associated with C5. In another embodiment of the invention, the present antibodies are used as adjunctive therapy with any other agent or any other therapy known to those skilled in the art useful for treating or ameliorating a disease or disorder associated with 05. Combination Therapies Combination therapies may include an anti-C5 antibody of the invention and any additional therapeutic agent that may be advantageously combined with an antibody of the invention, or with a biologically active fragment of an antibody of the invention. The antibodies of the present invention can be combined synergistically with one or more drugs or therapies used to treat a disease or disorder associated with C5. In some embodiments, the antibodies of the invention may be combined with a second therapeutic agent to improve one or more symptoms of said disease. Depending on the disease or disorder associated with C5, 109 the antibodies of the present invention can be used in combination with one or more additional therapeutic agents including, but not limited to an anticoagulant (for example, warfarin, aspirin, heparin, phenindione, fondaparinux, idraparinux, and thrombin inhibitors such as argatroban, lepirudin, bivalirudin, or dabigatran), an anti-inflammatory drug (e.g., corticosteroids, and non-spheroidal anti-inflammatory drugs), an anti-hypertensive (e.g., an angiotensin-converting enzyme inhibitor), an immunosuppressive agent ( for example, vincristine, cyclopsorin A, or methotrexate), a fibrinolytic agent (for example, ancrod, e-aminocaproic acid, antiplasmin-ai, prostacyclin, and defibrotide), a hypolipcmiantc agent such as hydroxymethylglutaryl CoA reductase inhibitor, an anti- CD20 such as rituximab, an anti-TNF agent such as infliximab, an anticonvulsant agent (for example, magnesium sulfate), a C3 inhibitor, or an antithrombotic agent. In certain embodiments, the second therapeutic agent is another antibody to the C5 protein. It is contemplated herein to use a combination (cocktail) of antibodies with broad neutralization or inhibitory activity against C5. In some embodiments, the non-competitive antibodies can be combined and administered to a subject in need of the 07 / I ηη / Ρ7Π7 / Β / ν 110 same. In some embodiments, antibodies comprising the combination bind to different non-overlapping epitopes on the protein. Antibodies comprising the combination may block C5 binding to C5 convertase and / or may prevent / inhibit the cleavage of C5 into C5a and C5b. In certain embodiments, the second antibody may possess a longer half-life in human serum. As used herein, the term in combination with means that additional therapeutically active components may be administered before, simultaneously with, or after administration of the anti-C5 antibody of the present invention. The term in combination with also includes the sequential or concomitant administration of an anti-C5 antibody and a second therapeutic agent. The additional therapeutically active component may be administered; to a subject; prior to administration of an anti-C5 antibody of the present invention. For example, a first component may be considered to be administered before a second component if the first component is administered 1 week before, 72 hours before, 60 hours before, 48 hours before, 36 hours before, 24 hours before, 12 hours before , 6 hours before, 5 hours before, 4 hours before, 3 hours before, 2 hours before, 1 hour before, 30 minutes before, 15 07 / I ηη / Ρ7Π7 / Β / ν 111 minutes before, 10 minutes before, 5 minutes before or less than one minute before the administration of the second component. In other embodiments, the additional therapeutically active component may be administered to a subject following administration of an anti-C5 antibody of the present invention. For example, a first component may be considered to be administered after a second component if the first component is administered 1 minute later, 5 minutes later, 10 minutes later, 15 minutes later, 30 minutes later, 1 hour later, 2 hours later , 3 hours later, 4 hours later, 5 hours later, 6 hours later, 12 hours later, 24 hours later, 36 hours later, 48 hours later, 60 hours later, 72 hours after administration of the second component. In still other embodiments, the additional therapeutically active component may be administered to a subject concurrent with the administration of an anti-C5 antibody of the present invention. Concurrent administration for purposes of the present invention includes, for example, administration of an anti-C5 antibody and an additional therapeutically active component to a subject in a single dosage form, or in separate dosage forms administered to the subject within about 30 minutes. or less with each other. If administered in separate dosage forms, each form of 112 dosage can be administered by the same route (for example, in anti-C5 antibody and the additional therapeutically active component can be administered intravenously, etc.); Alternatively, each dosage form may be administered by a different route (for example, the anti-C5 antibody may be administered intravenously, and the additional therapeutically active component may be administered orally). In any case, administering the components in an ionic dosage form, in separate dosage forms by the same route, or in separate dosage forms by different routes are all considered concurrent administration for purposes of the present disclosure. For purposes of the present disclosure, the administration of an anti-C5 antibody before, concurrent with or after (as those terms are defined herein) an additional therapeutically active component is considered administration of an anti-C5 antibody in combination with an additional therapeutically active component. The present invention includes pharmaceutical compositions in which an anti-C5 antibody of the present invention is co-formulated with one or more of the additional therapeutically active components as set forth 07 / I ηη / Ρ7Π7 / Β / ν 113 described in this document. Administration Regimes According to certain embodiments, a single dose of anti-C5 antibody of the invention (or pharmaceutical composition comprising a combination of an anti-C5 antibody and any of the therapeutically active agents mentioned herein) can be administered to a subject who need it. According to certain embodiments of the present invention, multiple doses of an anti-C5 antibody (or a pharmaceutical composition comprising a combination of an anti-C5 antibody and any of the additional therapeutically active agents mentioned herein) can be administered to a subject during a defined time course. Methods according to this aspect of the invention comprise sequentially administering to a subject multiple doses of an anti-C5 antibody of the invention. As used herein, administer sequentially means that each dose of an anti-C5 antibody is administered to a subject at a different point in time, e.g., on different days separated by a predetermined interval (e.g., hours, days, weeks, or months). The present invention includes methods comprising sequentially administering to the patient a single initial dose of an anti-C5 antibody, 114 followed by one or more secondary doses of the anti-C5 antibody, and optionally followed by one or more tertiary doses of the anti-C5 antibody. The terms initial dose, secondary doses and tertiary doses refer to the temporal sequence of administration of the anti-C5 antibody of the invention. Therefore, the initial dose is the dose that is administered at the beginning of the treatment regimen (also referred to as the baseline dose); secondary doses are doses that are administered after the initial dose; and tertiary doses are doses that are administered after secondary doses. The initial, secondary and tertiary doses may contain the same amount of anti-C5 antibody, but generally may differ from each other in terms of frequency of administration. In certain embodiments, however, the amount of anti-C5 antibody contained in the initial, secondary and / or tertiary dose vary from each other (e.g., adjusted up or down as appropriate) during the course of treatment. In certain embodiments, two or more (e.g., 2, 3, 4, or 5) doses are administered at the beginning of the treatment regimen as a loading dose followed by subsequent doses that are administered on a less frequent basis (e.g., 07 / I ηη / Ρ7Π7 / Β / ν maintenance dose). 115 In certain exemplary embodiments of the present invention, each secondary and / or tertiary dose is administered 1 to 48 hours (e.g., 1, 14, 2, 24, 3, 34, 4, 44, 5, 54, 6). , 64, 7, 74, 8, 84, 9, 94, 10, 104, 11, 11 4, 12, 124, 13, 134, 14, 144, 15, 154, 16, 164, 17, 174, 18, 184, 19, 194, 20, 204, 21, 21 4, 22, 224, 23, 23 4, 24, 244, 25, 25 4, 26, 264 or more) after the immediately preceding dose. The phrase immediately preceding dose, as used herein, means, in a sequence of multiple administrations, the dose of anti-C5 antibody that is administered to a patient prior to the administration of the next dose in the sequence without intervening doses. . Methods according to this aspect of the invention may comprise administering to a patient any number of secondary and / or tertiary doses of an anti-C5 antibody. For example, in certain embodiments, only a single secondary dose is administered to a patient. In other embodiments, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, or more) secondary doses are administered to a patient. Also, in certain embodiments, only a single tertiary dose is administered to a patient. In other embodiments, two or more (e.g., 2, 3, 4, 5, 6, 7 or more) tertiary doses are administered to a patient. In certain embodiments of the invention, the frequency 116 in which secondary and / or tertiary doses are administered to a patient may vary over the course of the treatment regimen. The frequency of administration may also be adjusted during the course of treatment by a physician depending on the needs of the individual patient following clinical examination. Diagnostic Uses of Antibodies The anti-C5 antibodies of the present invention can be used to detect and / or measure C5 in a sample, for example, for diagnostic purposes. Some embodiments contemplate the use of one or more antibodies of the present invention in assays to detect a C5-associated disease or disorder. Exemplary diagnostic assays for C5 may comprise contacting a sample, obtained from a patient, with an anti-C5 antibody of the invention, where the anti-C5 antibody is labeled with a detectable tag or reporter molecule or used as a capture ligand to selectively isolate C5 from patient samples. Alternatively, an unlabeled anti-C5 antibody can be used in diagnostic applications in combination with a secondary antibody that is detectably labeled. The detectable tag or reporter molecule can be a radioisotope3H,i4C,32P,35S, ori25I; a fluorescent or chemiluminescent moiety such as □7 / 1 nn / C7n7 / B / v isothiocyanate 117 fluorescein or rhodamine; or an enzyme such as alkaline phosphatase, β-galactosidase, horseradish peroxidase, or luciferase. Specific exemplary assays that can be used to detect or measure C5 in a sample include enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), and fluorescence-activated cell sorting (FACS). Samples that may be used in C5 diagnostic assays in accordance with the present invention include any tissue or fluid sample obtainable from a patient, which contains detectable amounts of C5 protein, or fragments thereof, under normal or pathological conditions. Generally, the levels of C5 protein in a particular sample obtained from a healthy patient (for example, a patient who does not suffer from a disease associated with C5) will be measured to initially establish a baseline level, or standard level, of C5. This reference level of C5 can then be compared with C5 levels measured in samples obtained from individuals suspected of having a condition associated with C5, or symptoms associated with such a condition. Antibodies specific for the C5 protein may contain no additional markers or residues, or may contain an N-terminal or C-terminal marker or residue. In a 118 embodiment, the label or remainder is bictin. In a binding assay, the location of a tag (if one exists) can determine the orientation of the peptide with respect to the surface on which the peptide binds. For example, if a surface is coated with avidin, a peptide containing an N-terminal biotin will be oriented such that the C-terminal portion of the peptide will be distal to the surface. Selected Realizations Selected embodiments of the present disclosure include the following: In Embodiment 1, the present invention includes an isolated antibody or antigen-binding fragment thereof that specifically binds to the complement factor 5 (C5) protein, wherein the antibody or antigen-binding fragment thereof interacts with one or more amino acids contained in C5 (SEQ ID NO: 359) as determined by hydrogen / deuterium exchange. In Embodiment 2, the present invention includes the antibody isolated from the antigen-binding fragment of Embodiment 1, wherein the antibody or antigen-binding fragment interacts with one or more amino acids contained within the alpha chain and / or beta chain of C5, as determined by hydrogen / deuterium exchange. 119 In Embodiment 3, the present invention includes the antibody isolated from the antigen-binding fragment of Embodiments 1 or 2, wherein the antibody or antigen-binding fragment does not interact with an amino acid of the C5a anaphylatoxin region of C5, as determined by hydrogen / deuterium exchange. In Embodiment 4, the present invention includes the antibody isolated from the antigen-binding fragment of Embodiments 1 to 3, wherein the antibody or antigen-binding fragment interacts with one or more amino acids contained within SEQ ID NO: 360 and / or SEQ ID Nc361, as determined by hydrocene / deuterium exchange. In Embodiment 5, the present invention includes the antibody isolated from the antigen-binding fragment of Embodiments 1 to 4, wherein the antibody or antigen-binding fragment interacts with an amino acid sequence selected from the group consisting of (a) the amino acids 591 to 599 of SEQ ID NO: 359; (b, amino acids 593 to 599 of SEQ ID NO: 359; ic) amino acids 775 to 787 of SEQ ID NO: 359; (d) amino acids 775 to 794 of SEQ ID NO: 359; and (e) amino acids 779 to 787 of SEQ ID NO: 359. In Embodiment 6, the present invention includes the isolated antibody or antigen binding fragment thereof from any of Embodiments 1 to 5, wherein the 07 / I ηη / Ρ7Π7 / Β / ν 120 antibody or antigen-binding fragment thereof interacts with at least five amino acids contained within 07 / I ηη / Ρ7Π7 / Β / ν of a sequence of amino acids selected from the group consisting of SEQ ID NO: 360 and 361. In Embodiment 7, the present invention includes the isolated antibody or antigen-binding fragment thereof from any of Embodiments 1 to 5, wherein the antibody or antigen-binding fragment thereof interacts with the amino acid sequences of SEQ ID No.: 360 and 361. In Embodiment 8, the present invention includes an isolated antibody or antigen-binding fragment thereof that specifically binds to the complement factor 5 (C5) protein, wherein the antibody or antigen-binding fragment interacts with the minus one of the following amino acid residues: N591, M592, A593, T594, G595, M596, D597, S598, 7 / 599, 7 / 775, E776, V777, H778, L77 9, V780, P781, R782, R783, K784, Q785, L786, Q787, F788, A789, L790, P791, D792, S793 or L794 of SEQ ID NO: 359. In Embodiment 9, the present invention includes the isolated antibody or antigen-binding fragment of any one of Embodiments 1 to 8, wherein the antibody has one or more of the following characteristics: (a) it has a serum concentration of more than 10 pg / ml until day 70 121 after administration to a cynomolgus monkey; (b) blocks classical pathway (CP) hemolysis until day 35 after administration to a cynomolgus monkey, as measured in an ex vivo hemolysis assay; (c) blocks alternative pathway (AP) hemolysis until day 35 after administration to a cynomolgus monkey, as measured in an ex vivo hemolysis assay; (d) has a serum half-life of more than 10 days in the cynomolgus monkey; (e) has a serum concentration of more than 10 gg / ml until day 40 after administration to C5-humanized mice; (f) blocks hemolysis by CP until day 30 after administration to C5-humanized mice, as measured in an ex vivo hemolysis assay; and (g) has a serum half-life of more than 10 days in C5-humanized mice. In Embodiment 10, the present invention includes the isolated antibody or antigen-binding fragment thereof from any of Embodiments 1 to 9, wherein the antibody has an additional characteristic selected from the group consisting of: (a) it is a monoclonal antibody completely human; (b) binds to human C5 with a dissociation constant (Kd) of less than 0.9 nM at 25°C, as measured in a surface plasmon resonance assay; (c) binds to human C5 with a Kd of less than 0.3 nM at 37 °C, as measured in a plasmon resonance assay 122 surface; (d) binds to monkey C5 with a Kd of less than 65 nM, as measured in a surface plasmen resonance assay; (e) binds to the human C5 variant R885H (SEQ ID NO: 356) with a Kd of less than 0.5 nM, as measured in a surface plasmen resonance assay; (f) binds to the human C5 variant R885C (SEQ ID NO: 357) with a Kd of less than 0.5 nM, as measured in a surface plasmen resonance assay; (g) blocks human-mediated classical pathway (CP) hemolysis by more than 95% and with IC50 less than 6 nM, as measured in a CP hemolysis assay; (h) blocks human C5-mediated alternative pathway (AP) hemolysis by more than 70% and with IC50 less than 165 nM, as measured in an AP hemolysis assay; (i) inhibits C5-mediated CP hemolysis of the African green monkey with IC50 of less than 185 nM, as measured in a CP hemolysis assay; (j) inhibits C5-mediated AP hemolysis of the African green monkey with IC50 of less than 235 nM, as measured in an AP hemolysis assay; (k) inhibits C5-mediated CP hemolysis of the African green monkey with IC50 of less than 145 nM, as measured in a CP hemolysis assay; and (1) inhibits C5-mediated AP hemolysis of the African green monkey with IC50 of less than 30 nM, as measured in an AP hemolysis assay. In Embodiment 11, the present invention includes the 123 isolated antibody or antigen-binding fragment of any of Embodiments 1 to 10, wherein the antibody or antigen-binding fragment comprises three heavy chain complementarity determining regions (CDR) (HCDR1, HCDR2 and HCDR3) contained within from any of the heavy chain variable region (HCVR) sequences listed in Table 1; and three light chain CDRs (LCDR1, LCDR2, and LCDR3) contained within any of the light chain variable region (LCVR) sequences listed in Table 1. In Embodiment 12, the present invention includes the isolated antibody or antigen binding fragment thereof from any of Embodiments 1 to 11, comprising: (a) an HCDR1 domain having an amino acid sequence selected from the group consisting of SEQ ID NO: 4, 20, 36, 52, 68, 84, 100, 124, 140, 148, 156, 172, 188, 204, 220, 236, 252, 268, 276, 292, 308, 324 and 340; (b) an HCDR2 domain having an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 22, 38, , 70, 86, 102, 126, 142, 150, 158, 174, 190, 206, 222, 238, 254, 270, 278, 294, 310, 326 and 342; (c) an HCDR3 domain having an amino acid sequence selected from the group consisting of SEQ ID NO: 8, 24, 40, 56, 72, 88, 104, 128, 144, 152, 160, 176, 192, 208, 224 240, 256, 272, 280, 296, 07 / I ηη / Ρ7Π7 / Β / ν 124 312, 328 and 344; (d) an LCDR1 domain having an amino acid sequence selected from the group consisting of SEQ ID NO: 12, 28, 44, 60, 76, 92, 108, 116, 132, 164, 180, 196, 212, 228 , 244, 260, 284, 300, 316, 332 and 348; (e) an LCDR2 domain having an amino acid sequence selected from the group consisting of SEQ ID NO: 14, 30, 46, 62, 78, 94, 110, 118, 134, 166, 182, 198, 214, 230 , 246, 262, 286, 302, 318, 334 and 350; and (f) an LCDR3 domain having an amino acid sequence selected from the group consisting of SEQ ID NO: 16, 32, 48, 64, 80, 96, 112, 120, 136, 168, 184, 200, 216, 232, 248, 264, 288, 304, 320, 336 and 352. In Embodiment 13, the present invention includes the isolated antibody or antigen-binding fragment thereof from any of Embodiments 1 to 12 comprising an HCVR having an amino acid sequence selected from the group consisting of the HCVR sequences listed in Table 1. In Embodiment 14, the present invention includes an isolated antibody or antigen-binding fragment thereof from Embodiment 13 comprising an LCVR having an amino acid sequence selected from the group consisting of LCVR sequences listed in Table 1. In Embodiment 15, the present invention includes the isolated antibody or antigen binding fragment of 125 any of embodiments 11 to 14 comprising a pair of HCVR / LCVR amino acid sequences selected from the group consisting of SEQ ID NO: 2 / 10, 18 / 26, 34 / 42, 50 / 58, 66 / 74 , 82 / 90, 98 / 106, 98 / 114, 122 / 106, 98 / 130, 138 / 106, 146 / 106, 122 / 130, 146 / 114, 146 / 130, 138 / 130, 154 / 162, 170 / 178, 186 / 194, 202 / 210, 218 / 226, 234 / 242, 250 / 258, 266 / 258, 274 / 282, 290 / 298, 306 / 314, 322 / 330 and 338 / 346. In Embodiment 16, the present invention includes the isolated antibody or antigen-binding fragment thereof from any of Embodiments 11 to 15 comprising three CDRs contained within an HCVR selected from the group consisting of SEQ ID NO: 50, 98, 138, and 202; and three CDRs contained within an LCVR selected from the group consisting of SEQ ID NO: 58, 106 and 210. In Embodiment 17, the present invention includes the isolated antibody or antigen-binding fragment thereof of Embodiment 16 comprising CDRs selected from the group consisting of: (a) SEQ ID NO: 52, 54, 56, 60, 62, and 64; (b) SEQ ID NO: 100, 102, 104, 108, 110 and 112; (c) SEQ ID NO: 140, 142, 144, 108, 110 and 112; and (d) SEQ ID NO: 204, 206, 208, 212, 214 and 216. In Embodiment 18, the present invention includes the isolated antibody or antigen binding fragment thereof of Embodiment 17 comprising a pair of 126 amino acid sequences of HCVR / LCVR selected from the group consisting of SEQ ID NO: 50 / 58, 98 / 106, 138 / 106 and 202 / 210. In Embodiment 19, the present invention includes an antibody or antigen-binding fragment thereof that competes for binding to C5 with the antibody or antigen-binding fragment of Embodiment 17. In Embodiment 20, the present invention includes an antibody or antigen-binding fragment thereof that binds to the same epitope as an antibody or antigen-binding fragment of Embodiment 17. In Embodiment 21, the present invention includes the antibody or its antigen-binding fragment thereof of Embodiment 9 or 10 comprising a sin chain variable region comprising an amino acid sequence listed in Table 1 having no- more of 5 amino acid substitutions. In Embodiment 22, the present invention includes the antibody or antigen binding fragment thereof of Embodiment 21, which comprises a light chain variable region comprising an amino acid sequence listed in Table 1 having no more than 5 amino acid substitutions. In Embodiment 23, the present invention includes the antibody or antigen binding fragment thereof of 07 / I ηη / Ρ7Π7 / Β / ν 127 Embodiment 9 or 10 comprising a heavy chain variable region that has at least 90% sequence identity with SEQ ID NO: 98. In Embodiment 24, the present invention includes an antibody or antigen-binding fragment thereof of Embodiment 23 comprising a light chain szarable region having at least 90% sequence identity with SEQ ID NO: 106 . In Embodiment 25, the present invention includes an isolated monoclonal antibody or an antigen-binding fragment thereof that blocks cleavage of C5 to C5a and C5b comprising three CDRs of an HCVR, wherein the HCVR has an amino acid sequence selected from group consisting of SEQ ID NO: 2, 18, 34, 50, 66, 82, 98, 122, 138, 146, 154, 170, 186, 202, 214, 234, 250, 266, 274, 290, 306 , 322 and 338; and three CDRs of an LCVR, where the LCVR has an amino acid sequence selected from the group consisting of SEQ ID NO: 10, 26, 42, 58, 74, 90, 106, 114, 130, 162, 178, 194, 210, 226, 242, 258, 282, 298, 314, 330 and 346. In Embodiment 26, the present invention includes a pharmaceutical composition comprising an isolated antibody or an antigen-binding fragment thereof that binds to C5 according to any of Embodiments 1 to 25 and a pharmaceutically acceptable carrier or diluent. 07 / I ηη / Ρ7Π7 / Β / ν 128 In Embodiment 27, the present invention includes an isolated polynucleotide molecule comprising a polynucleotide sequence encoding an HC3 / R of an antibody as set forth in any of embodiments 1 to 2 5. In Embodiment 28, the present invention includes an isolated polynucleotide molecule comprising a polynucleotide sequence encoding an LCVR of an antibody as set forth in any of Embodiments 1 to 25. In Embodiment 29, the present invention includes a vector comprising the polynucleotide sequence of Embodiment 27 or 28. In Embodiment 30, the present invention includes a cell that expresses the vector of Embodiment 29. In Embodiment 31, the present invention includes a method for preventing, treating or ameliorating at least one symptom or indication of a disease or disorder associated with C5, the method comprising administering an antibody or an antigen-binding fragment of any of Embodiments 1 25 to a subject who needs the same. In Embodiment 32, the present invention includes the method of Embodiment 31, where the disease or disorder is selected from the group consisting of uremic syndrome 129 atypical hemolytic (aHUS), parodistic nocturnal hemoglobinuria (PNH), age-related macular degeneration, geographic atrophy, uveitis, neuromyelitis optica, multiple sclerosis, stroke, Guillain Barre syndrome, traumatic brain injury, Parkinson's disease, sleep disorders inappropriate or unwanted complement activation, hemodialysis complications, hyperacute allograft rejection, xenograft rejection, interleukin-2-induced toxicity during IL 2 therapy, inflammatory disorders, inflammation of autoimmune diseases, Crohn's disease, distress syndrome respiratory in adults, thermal injuries including burns or frostbite, post-ischemic reperfusion conditions, myocardial infarction, capillary leak syndrome, obesity, diabetes, Alzheimer's disease, schizophrenia, stroke, epilepsy, atherosclerosis, vasculitis, bullous pemphigoid, glomerulopathy C3, membranoproliferative glomerulonephritis, diabetic nephropathy, Alport syndrome, progressive renal failure, proteinuric kidney disease, renal ischemia-reperfusion injury, lupus nephritis, balloon angioplasty, post-pump syndrome in cardiopulmonary bypass or renal bypass, hemodialysis, renal ischemia , mesenteric artery reperfusion after aortic reconstruction, 07 / I ηη / Ρ7Π7 / Β / ν 130 infectious disease or sepsis, immune complex disorders and autoimmune diseases, kidney disorders, rheumatoid arthritis, systemic lupus erythematosus (SLE), SLE nephritis, proliferative nephritis, hemolytic anemia, asthma, chronic obstructive pulmonary disease (COPD), emphysema, stroke and pulmonary infarctions, pneumonia and myasthenia gravis. In Embodiment 33, the present invention includes the method of Embodiment 31, where the disease or disorder is aHUS. In Embodiment 34, the present invention includes the method of Embodiment 31, where the disease or disorder is PNH. In Embodiment 35, the present invention includes the method of any of Embodiments 31 to 34, in which the pharmaceutical composition is administered prophylactically or therapeutically to the subject in need thereof. In Embodiment 36, the present invention includes the method of any of Embodiments 31 to 35, wherein the pharmaceutical composition is administered in combination with a second therapeutic agent. In Embodiment 37, the present invention includes the method of Embodiment 36, where the second therapeutic agent 07 / I ηη / Ρ7Π7 / Β / ν 131 is selected from the group consisting of an anticoagulant, an anti-inflammatory drug, an antihypertensive, an immunosuppressive agent, a lipid-lowering agent, an anti-CD20 agent such as rituximab, an anti-TNF agent, such as infliximab, an anticonvulsant agent, an inhibitor of C3, a second anti-C5 antibody and an anti-thrombotic agent. In Embodiment 38, the present invention includes the method of any of Embodiments 31 to 37, wherein the pharmaceutical composition is administered subcutaneously, intravenously, intradermally, intraperitoneally, orally, intramuscularly or intracranially. EXAMPLES The following examples are presented to provide those skilled in the art with a complete disclosure and description of how to make and use the methods and compositions of the invention, and are not intended to limit the scope of what the inventors consider to be their invention. Efforts have been made to ensure accuracy with respect to numbers used (e.g. quantities, temperature, etc.), but some experimental errors must be considered. Unless otherwise noted, parts are parts by weight, molecular weight is average molecular weight, temperature is in degrees Celsius, room temperature is 132 approximately 25 °C and the pressure is at or close to atmospheric. Example 1: Generation of human antibodies to complement the factor 5 (C5) protein Human antibodies to the C5 protein were generated in a VELOCIMMUNE® comprising DNA encoding kappa heavy and light chain variable region immunoglobulin. Mice were immunized with purified human C5 protein in serum (Calbiochem Cat # 20-4888). The antibody immune response was monitored by a C5-specific immunoassay. When a desired immune response was achieved, splenocytes were harvested and fused with mouse myeloma cells to preserve their viability and form hybridoma cell lines. Hybridoma cell lines were screened and screened to identify cell lines that produce C5-specific antibodies. The cell lines were used to obtain various chimeric anti-C5 antibodies (i.e., antibodies possessing human variable domains and mouse constant domains); Exemplary antibodies generated in this way were designated as H2M11683N and H2M11686N. Anoi-C5 antibodies were also isolated directly from antigen-positive mouse B cells without 133 fusion to myeloma cells, as described in US Patent 7582298, specifically incorporated herein by reference in its entirety. Using this method, several fully human anti-C5 antibodies (i.e., antibodies possessing human variable domains and human constant domains) were obtained; Exemplary antibodies generated in this way were designated as H4H12159P, H4H12161P, H4H12163P, H4H12164P, H4H12166P, H4H12167P, H4H12168P, H4H12169P, H4H12170P, H4H12171P, H4H12175P, H 4H12176P2, H4H12177P2, and H4H12183P2. The biological properties of exemplary antibodies generated according to the methods of this Example are described in detail in the Examples set forth below. Example 2: Amino acid and nucleotide sequences of the variable region of the heavy and light chain Table 1 sets forth the amino acid sequence identifiers of the heavy and light chain variable regions and CDRs of selected anti-C5 antibodies of the invention. Table 1: Amino acid sequence identifiers 134 SEQ ID NOs: Antibody Designation IICVR HCDR1 IICDR2 HCDR3 LCVR LCDR1 LCDR2 LCDR3 H2M1 1683N 2 4 6 8 10 12 14 16 H2M11686N 18 20 22 24 26 28 30 32 H4II12159P 34 36 38 40 42 44 46 48 H4H12161P 50 52 54 56 58 60 62 64 H4H12163P 66 68 70 72 74 76 78 80 ~ Η4Ι112Ϊ64Ρ ~ 82 84 । ~ 86 88 ~ 90 92 94 9(> H4H12166P 98 100 102 104 106 108 lio 112 H4H12166P2 98 100 102 104 114 ! 116 1 118 120 11411121661b 122 12 4 126 128 106 108 110 112 ~H4H I2166P4 ' ' 98 GONE 102 104 130 132 ' 134 Ú6 H4H12166P5 138 140 142 144 106 108 110 112 H4H12166P6 146 148 150 152 106 108 i 110 112 ÍI4H12166P7 122 124 126 128 13 0 132 134 136 H4H12166P8 146 148 150 152 114 116 118 120 H4H12166P9 146 148 150 152 130 ; 132 134 136 H4H12166P10 138 140 142 144 130 132 134 136 H4H12167P 154 156 158 160 162 164 166 168 07 / I ηη / Ρ7Π7 / Β / ν H4H12168P 170 172 174 176 178 180 182 184 H4H12169P 186 188 190 192 194 196 198 200 ._____ ___ ________— ______ _____ H4H12170P 202 204 206 208 210 21 2 214 216 H4H iTlYlF 218 220 ~ 222 224 226 228 230 232 H4H12175P 234 236 238 240 242 244 246 248 H4H12176P2 250 252 254 256 258 260 262 264 H4H12177P2 266 268 270 272 258 260 262 264 II41I12183P2 274 276 ~ 278 ~ 280 282 284 286 288 H2M11682N 290 292 294 296 298 ; 300 302 304 H2M1 1684N 306 308 310 312 314 ' 316 318 320 H2M11694N 322 324 326 328 330 7 332 334 336 H2MH695N 338 340 342 344 34 6 ; 348 J_______ 350 352 The corresponding nucleic acid sequence identifiers are set out in Table 2. 135 Table 2: Nucleic Acid Sequence Identifiers □7 / 1 nn / C7n7 / B / viAi Antibody Designation HCVR IICDR1 SEQ ID NOs: LCDRl LCDR3 HCDR2 HCDR3 LCVR LCDRl Η2Μ11683Ν I 3 5 7 9 11 13 15 712m11686N¿ 17 19 21 23 25 27 29 31 ~ H4H12159P 33 35 37 39 4 1 43 45 47 H4HÍ2161P 49 51 53 55 57 59 61 63 H4H12163P 65 67 69 71 73 75 77 79 H4H12164P 81 83 85 87 89 91 93 95 H4H12166P 97 99 101 103 105 107 109 111 H4H12166P2 97 99 < 101 103 113 115 117 119 H4II12166P3 121 123 125 127 105 107 109 111 II4H12166P4 97 99 101 103 129 131 133 135 H4H12166P5 137 139 141 143 105 107 109 111 H4H12166P6 145 147 149 151 105 107 109 111 H4H12166P7 121 123 125 127 129 131 133 135 H4H12166P8 145 147 149 151 113 117 119 H4H12166P9 145 147 149 151 129 131 133 135 H4H12166P10” 137 139 141 143 129 iñ 133 135 H4H12167P 153 155 157 159 161 - - _____ 163 165 167 H4H12168P 169 171 173 175 177 179 181 183 H4H12169P 185 187 189 191 193 195 197 199 H4H12170P 201 203 205 207 209 21E 213 215 H4H12171P 217 219 221 223 225 227 229 231 F14H12175P 233 235 237 239 241 243 245 247 H4H12176P2 249 251 253 255 257 259 261 263 H4H12177P2 265 267 269 271 257 259 261 263 H4H12183P2 273 275 277 279 281 283 285 287 H2M11682N 289 291 293 295 297 299 301 303 1I2M11684N 305 307 309 311 313 315 317 319 H2M11694N 321 323 325 32 7 329 331 333 335 H2M11695N 337 339 341 343 345 347 349 351 136 Antibodies are typically referred to herein according to the following nomenclature: Fe prefix (e.g., H4H, H2M, etc.), followed by a numerical identifier (e.g., 11686, 12166, 12183 etc., as shown in Table 2), followed by a suffix P, P2 or N. Therefore, according to this nomenclature, an antibody may be referred to herein as, for example, H2M11686N, H4H12183P2, H4H12168P, etc. The prefixes H4H and H2M in the antibody designations used herein indicate the particular isotype of the Fe region of the antibody. For example, an H4H antibody has a human IgG4 Fe that comprises a serine to proline mutation in the hinge region (S108P). to promote dimer stabilization, and an H2M antibody has a mouse IgG2 Fe (isotype a or b) (all variable regions are completely human as indicated by the first H in the antibody designation). As one skilled in the art will appreciate, an antibody having a particular Fe isotype can be converted to an antibody with a different Fe isotype (for example, an antibody with a mouse IgGl Fe can be converted to an antibody with a human IgG4, etc.), but in any case, the variable domains (including CDRs), indicated by the numerical identifiers shown in the 137 Table 2, will remain the same, and the antigen binding properties are expected to be identical or substantially similar regardless of the nature of the Fe domain. In certain embodiments, antibodies selected with a mouse IgGl Fe were converted to antibodies with human IgG4 Fe. In one embodiment, the Fe IgG4 domain comprises 2 or more amino acid changes as disclosed in US20100331527. To generate mutated antibodies, several residues in the complementary determining regions (CDRs) of H4H12166P were mutated to histidine to generate 9 mutated antibodies, identified as H4H12166P2 to H4H12166P10. Histidine mutations in CDRs have been shown to confer a ρΗ dependence of target antigen binding leading to improved pharmacokinetics (Igawa et al. 2010, Nat. Biotechnol. 28: 1203-1207). Control Constructs Used in the Following Examples The following control constructs (anti-C5 antibodies) were included in the experiments disclosed herein for comparative purposes: Comparator 1, a monoclonal antibody against human C5 having Vh / Vl sequence of h5Gl.l antibody according to US Patent No. 6,355,245 (Alexion Pharmaceutica1s, Inc.) and Comparator 2, 138 a human monoclonal antibody against human C5 having Vh / Vl sequences of antibody 8109 according to US Patent Application Publication No. 2013 / 0022615 (Novartis). Example 3. Antibody binding to C5 as determined by Surface Plasmon Resonance Equilibrium dissociation constants (Kd values) for C5 binding to purified anti-C5 antibodies were determined using a real-time surface plasmon resonance biosensor assay on a Biacore T200 instrument. The Biacore sensor surface was derived by amine coupling with a mouse monoclonal anti-human Fc antibody (GE Healthcare, #BR-1008-39) to capture anti-C5 antibodies expressed with human Fe constant regions. Biacore binding studies were performed in HBST Run Lamp (0.01 M HEPES, pH 3.4, 0.15 M NaCl, 3 mM EDTA, 0.05% v / v Surfactant P20). Human C5 was obtained from a commercial source (EME). Other C5 reagents were expressed with a C-terminal mycmyc-nexahistidine tag (later named C5mmh). Human C5 mmh reagents containing histidine and cysterna point mutations at arginine 885 (later named C5 R885H-mmh and C5 07 / I ηη / Ρ7Π7 / Β / ν R885C—mmh, respectively). Different concentrations of C5 139 human, C5 R885H-mmh human (SEQ ID NO: 356), C5 R885C-mmh human (SEQ ID NO: 357) and C5-mmh monkey (SEQ ID NO: 358) (varying from 100 to 1.23 nM, threefold dilutions) prepared in HBST were injected onto the captured surface with the anti-C5 antibody at a flow rate of 30 μΐ / min. The association of all C5 reagents to each of the captured monoclonal antibodies was monitored for 3 minutes and their dissociation in HBST Run Lamp was monitored for 8 minutes. All binding kinetics experiments were performed at 25°C or 37°C. Association kinetics (7:a) and dissociation rate constants (ba) were determined by fitting the real-time sensorgrams to a 1:1 binding model using Scrubbcr 2.0c curve fitting software. The dissociation equilibrium binding constants (Kd) and dissociative half-lives (tb) were calculated from the kinetic rate constants as: Kd (M) = kd / ka and t^ (min) = In2 / (60x kd) The binding kinetic parameters for the binding of human C5 to anti-C5 antibodies at 25°C and 37°C are shown in Tables 3 and 4. Table 3: Binding kinetic parameters of anti-C5 monoclonal antibodies binding to human C5 at 25°C 140 Antibody 1141111683 N 114HI2UIP Amount of Antibody Captured (RUI '231 51 1 OOnM C5 Human Bound 439 ' 64 64 96 A (1 / Ms) 4. i 7!··-05 1.49E105 ~~2.58ΕΓο5 ΤΓ36ΕΗ)5 1 4 _ 4- A (Us) 5 / Γ4ΐΤθ5 8.16E-05 4.37E-05 6.75E-05 KI) (\b 1.23F-E· 5.4OF-E· 2.0IE-1H 142 264 171 H4H12161P ~Η4ΗΪ2176Ι'Γ 38 50 H4H12163P 51 108 6.43Et05 2.08E-04 3.24E-10 55 H4H12167P 52 116 1.09Et06 1.31 E-04 1.21F-10 88 ~ H4H12175P~ ~ Too 2.16E-05 4- 1.96E-04 9.10E-1O ~ 59 H4H12159P 53 118 9.75E»05 7.13E-05 7.31 E-l 1 162 H4H12164P 52 103 2.92ΕΙΌ5 8.84E-05 3.02E-10 131 H4H12168P 50 113 4.23 Et 05 4.75E-05 1.12E- 10 243 H4HÍ2I69P ' 51 18 2.24EtoT TT40E-04 1.96E-09” ” 26 H4H11686N 200 341 2.20E-05 3.31 E-05 1.50E-10 349 H4H12170P 51 119 5.25E-05 6.79E-05 1.29E-10 170 H4ÍB2177P2 ' 47 60 6.561·.04 6.29E- 05 9.59E-10 184 1I4H12183P2 ~ 46 ' 50 1.66E05 2.70E-05 1.63E-10' 427 H4H12166P 53 105 6.42E-05 1.10E-04 1.71E-10 105 H4H12166P2 53 95 8.261W 05 3.61 E-04 4.38 E-10 32 H4H12166P3 i 59 124 4.03E+05 4.65E-04 1.15E-09 25 H4H12166P4 49 92 4.46IH05 1.76E-04 3.95E-10 66 H4H12166P5 59 110 2.85 E+05 3.28E-04 1.15E-09 35 H4H12166P6 64 131 4.89E + 05 i 1.84E-04 3.75E-10 63 H4H12166P7 50 92 2.74E + 05 I 1.0IE-03 3.67E-09 11 H4H12166P8 50 91 4.84E+05 6.86E-04 1.42E-09 17 H4H12166P9 52 100 3.32ΕΌ5 2.64E-04 7.94E-10 44 H4H12166P10 49 69 1.57Fx05 ! I.32E-03 8.38E-09 9 Comparator 1 232 250 ' V69Ü04’ 1.46E-04 1.51E-09 79' Comparator 2 117 170 2.62EtO5 2.39E-04 9.12E-10 48 Table 4: Binding kinetic parameters of anti-C5 monoclonal antibodies binding to human C5 at 37°C. 07 / I ηη / Ρ7Π7 / Β / ν 141 Antibody Quantity of .Antibody 1 OOnM C5 Human k. Á'd tu captured Kingdom (RU), (RU) (1 / Ms) (1 / s) (M) (min) H4H11683N 257 492 4.541-305 2.41E-04 5.32E-10 48 H4H12171P 59 58 * 1.221- 305 7.62E-04 6.27E-09 15 H4H12161P 4θ” 66 1.16F305 1.15E-04 9.90E-10 101 IΙ4Π 12176P2 38 71 i 1.47E+05 2.34E-04 L59E-09 49 ”H 4H12163P ' ​​65 139 9.111-305 6.65E-04 7.2913-10 17 H4H12167P 75 153 ' 1.291-3 06 3.81E-04 2.95E-10 30 H4H12175P 74 132 2.961-3 05 6.37E-04 2.15E-09 18 H4H12 159P 70 145 1.041-3 06 1.07E -04 1.03 E-10 108 H4H12164P 66 140 3.96F3 05 1.28E-04 3.23 E-10 90 H4IU2168P 34 -------- _ 59 12 ; 2.5013 04 ' 4.64E-04 ' Í.85E-08 25 H4H12169P 65 1.15F3 05 3.52E-04 3.06E-09 33 '11411116863 206 4'6 i 3.33 b+ 05 1.56E-04 4.69E-1 0 74 H4H12170P ' 34 A 2.971-3 05 ί- 4.421-3 04 Γ 4.30P3 04 ”4.15E-04 1.40E-09 28 ' H4H12177P2 41 . 37 5.78E-04 1.31E-O8 20 H4H12183P2 29 30 2.50E-04 5.81E-09 46 ' H4H12Í66P 127 8.80E t05 2.30E-04 2.62E-10 50 H4H12166P2 68 110 9 .501-305 + 6.12ΕΪ05 “Γ 5.051- 3 05 1.23E-03 1.29E-09 9 ; H4H12166P3 86 i 47 1.27E-03 2.07E-09 9 ! H4H12166P4 63 108 4.69E-04 9.30E-10 25 Γ H4H12166P5 76 129 4.40F3 05 1.22E-03 2.77E-09 9 H4H12166P6 90 157 ! 5.42E+05 U ---------- 3.49F3 05 4.74E-04 8.75E-10 24 H4H12166P7 64 105 2.58É-03 7.39E-09 4 H4H12166P8 65 98 í 6.751-3 05 2.09E- 03 3.10E-09 1.70E-09 6 1141112166P9 76 122 3.75F305 + ” 2.27ÍÑ05” 6.39E-04 18 H4H12166P10 64 82 3.14E-03 1.38E-O8 4 Comparator 1 185 24 6 1 1.4713 05 i 2.851-305 5.30E -04 3.61E-09 27 Comparator 2 119 205 6.57E-04 2.30E-10 18 The binding of monkey C5-mmh to anti-C5 antibodies at and 37 °C is shown in Tables 5 and 6. 142 Table 5. Binding kinetic parameters of anti-C5 monoclonal antibodies bound to monkey C5-mmh at 25°C. 07 / I ηη / Ρ7Π7 / Β / ν Antibody Amount of captured antibody (RU) 1 OOnM bound monkey C5-mmh (RU) ka (1 / Ms) kd (1 / s) Ád (M) 1½ (min) H4H11683N 228 403 3.86E-05 2.47E-04 6.40 E-10 47 H4H12171P 51 17 4.60E-04 2.26E-04 4.92E-09 51 H4H12161P 38 45 6.33ID04 2.48E-05 3.92E-10 465 H41I12176P2 50 69 1.82 FU 05 5.88E-05 3.22E-10 196 H4H12163P 50 98 3.1UD05 7.75E-04 2.49E-09 15 H4H12167P 52 111 4.19PN05 1.32E-04 3.15E-10 88 H4H12175P 51 59 6.42 ID 04 1.65E-03 2.57E-08 7 H 4H12159P 53 116 3.54E+05 4.69 E-05 1.33E-10 246 I14H12164P 51 66 1.27E i 05 1.53E-03 1.20E-08 8 H4H12168P 50 86 1.73ID05 1.14E-04 6.60E-10 101 H4H12169P 51 22 1.64E! 05 4.55E-03 2.78E-08 3 H4H11686N 196 247 1.57E · 05 4.89E-04 3.11E-09 24 H4H12170P 51 92 2.62ID05 5.2113-05 1.99E-10 222 H4H1217 7P2 47 32 4.62ID04 9.92E-04 2.15E -08 12 H4H12183P2 47 23 4.88ID04 4.94E-04 1.01E-08 23 H4H12166P 52 90 2.05E'05 1.06E-Ü3 5.15E-09 11 H4H12166P2 53 71 3.00ÍD 05 3.16E-03 1.05E-08 4 H4II12166P3 59 72 1.68E+05 4.47E-03 2.66E-08 3 H4H12166P4 49 69 2.1 OID 05 1.78E-03 8.50E-09 6 H4H12166P5 59 56 1.44ID05 3.46E-03 2.40E-08 3 H4 II12166P6 64 94 2.39E-05 2.66E-03 1.11 E-08 4 H4H12166P7 50 36 1.36E-05 6.33E-03 4.65E-08 2 H4H12166P8 50 47 2.31 ID 05 4.99E-03 2.16E-08 2 II4H12166P9 52 55 1.701D05 3.18E-03 1.87 E-08 4 II4II12166P10 49 15 9.56E · 04 6.16E-03 6.44E-08 2 Comparator 1 228 11 N / A N / A 3.11E-07 N / A N / A = Not Available; state 143 Table 6. Binding kinetic parameters of anti-C5 monoclonal antibodies binding to monkey C5-mmh at 37°C 07 / I ηη / Ρ7Π7 / Β / ν Antibody Quantity 1 OOnM KD t'A of C5-mmh bound captured monkey antibody (1 / Ms) (1 / s) (M) (min) (RU) II4H11683N 192 303 5.35EaO5 1.15 E-03 2.16E-09 10 H4H12171P 59 78 ' 5.56R105 1.03E-03 1.85E-09 11 H4H12161P 41 53 1.34E + 05 7.45E-04 5.56E-09 16 II4H12176P2 36 47 1.35E + 05 1. 29E-03 9.60E-09 9 H4H12163P 64 129 ' 3.90E + 05 1.25E-Ó3 3.20E-09 9 H4H12167P 74 146 5.37E*05 2.89E-04 5.39E-10 40 H4H12175P 74 74 1.77E-+05 2.76E-03 1.56E-08 4 H4H12159P 70 137 4.12E + 05 5.50E-05 1.33E-10 210 H4HI2164P 65 99 1.86E + 05 1.17E-03 6.30E-09 10 H4H12168P 34 29 5.33EI04 6.76E-04 1.27E-08 17 H4H12169P 59 64 2.51EI05 3.61 E-03 1.43E-08 3 H4II11686N 145 195 2.33E+05 2.07E-03 8.88E-09 6 H4H12170P 34 60 5.21E + 05 8.71E-04 1.67E-09 13 H4H12177P2 41 27 1.50E105 7.17E-03 4.77 E-08 2 H4H12183P2 28 13 ' 5.40EI04 6.37E-03 1.18E-07 2 H4H12166P 68 110 ¡ 2.19E+05 1.87E-03 8.55E-09 6 H4H12166P2 68 83 3.93EI05 2.97E-03 7.56E-09 4 H4H12166P3 85 92 2.23El 05 2.92E-03 1.31E-08 4 H4H12I66P4 62 80 ! 2.23EI05 1.83E-03 8.20E-09 6 H4H12166P5 75 70 1.50EH15 3.1313-03 2.09E-08 4 H4H12166P6 90 1 12 2.53EI05 2.32E-03 9.18E-09 H4H12166P7 63 48 ' 1.251b 05 2.41 E- 03 1931.-08 i 5 H4H12166P8 L . .. . 64 53 . 2.03EI05 2.69E-03 1.33E-08 4 H4II1216P9 75 69 1 1.81FO05 2.61 E-03 1.44E-08 4 H4H12166P10 63 24 6.601B 04 2.79E-03 4.22E-08 4. . ----- Comparator 1 132 4 ' ÑB NB NB Human R885H-mmh and human C5 R885C-mmh binding to anti-C5 antibodies are shown in Tables i and 8 respectively. 144 Table 7. Binding kinetic parameters of anti-C5 monoclonal antibodies binding to human C5 R885H-mmh at 25°C. Antibody Amount of antibody captured (RU) lOOnM C5 R885Hmmh Human bound (RU) k3 (1 / Ms) Ad (1 / s) Ad ' ' íMj 1½ (min) H4H11683N 183 118 5.26E i 05 2.46E-04 4.68E- 10 47 H4U12171P 119 51 6.59E4 05 1.42E-04 2.16E-10 81 H4I112161P 105 199 8.361x04 8.32E-05 9.96E-10 139 H4H12176P2 170 65 1.78 E-05 2.17E-04 1.22E-09 53 H4H12163P 111 214 6.72E-05 4.34E-04 6.46E-10 27 H4H12167P 93 187 6.89FN 05 2.98E-04 4.33E-10 39 H4H12175P 104 207 1.81 05 1.98E-03 1.09E-08 6 H 4H12I59P 101 177 7.06EI05 1.76E -04 2.50E-10 66 H4H12164P 143 295 1.58E + 05 1.87E-04 1.19E-09 62 H4H12168P 138 197 5.29EI04 2.14E-04 4.05E-09 54 H4H12169P 116 173: 4.84E105 7.09E-05 1.47E- 10 163 Η4Η11686Ν 145 259 2.16ΕΌ5 1.06E-04 4.91E-10 109 H4H12170P 244 442 4.09E-05 Η 1.61E-04 3.94E-10 72 H4H12177P2 137 232 1.481x05 5.92E-04 4.01E-09 20 H4H12183P2 158 99 3.771^04 4.37E-05 1.16E-09 264 H4H12166P 188 366 5.28EI05 2.12E-04 4.02E-10 54 Comparator 1 87 11 NB NB NB NB Comparator 2 118 249 1.08EI 06 6.53E -04 6.06E-10 18 145 Table 8. Binding kinetic parameters of anti-C5 monoclonal antibodies binding to human C5 R885C-mmh at 25°C. Antibody Amount of Antibody Captured (RU) 1 OOnM C5 R885Cmmh bound human Aa Ad A’o tb (1 / Ms) (1 / s) (M) (min) H4H11683N 174 116 4.99E · 05 2.39E-04 L_. _____ ... . 4.79E-10 48 H4H12171P 109 51 3.79E-05 1.39E-04 3.66E-10 83 H4H12161P 103 _ 147 1.3010 05 8.71E-05 6.72E-10 133 H4HÍ2Í76P2~ 164 63 Ε071-05 ~ ' 2Ί8Ε-04 2.03E -09 53 Η4Η12Ϊ63Ρ 110 211 5O4ÍÑ05-' ~4.32E-04 8.58E-10 27 H4H12167P 85 163 741EI05 2.94E-04 4.13E-10 39 Η41Π2175Ρ 99 128 8H8EH)4 1.55E-02 1.90E-07 1 1141I12159P 93 168 5.86EW5 1.6 9E-04 2.89E-10 68 114H12164P Ϊ39 249 1.53ER05 1.82E- 04 ~ ~ Í.19E-09 63 H4H12168P 128 144 6.09E! 04' 1.99E-04 3.27E-09 58 H4H12169P 108 168 2.78E-05 6.99E-05 2.5 mess 10 165 H4H11686N 143 253 1.78E05 9.49E-05 5.34E-10 122 H4H 12170P 244 427 3.57E-05 1.60E- 04 4.47E-10 72 H4H12177P2 138 177 1.00E * 05 1.32E-03 1.32E-08 9 H4H12183P2 158 80 2.99Et04 2.20E-05 7.37E-10 525 H4H12166P 188 356 4.26ER05 2.07E-04 4.87E-10 56 Comparator 1 87 9 NB Yb NB NB Comparator 2 117 241 L17E;06 649E-04 5.30E-10 19 The union of C5 R885H-mmh human and C5 R 8 8 5 -mmh human anti-Coa antibodies 3 / °C is shown in Tables 9 and 10, respectively. 146 Table 9. Binding kinetic parameters of anti-C5 monoclonal antibodies binding to human C5 R885H-mmh at 37°C. Antibody Amount of Antibody captured (RU) 1OOnM C5 R885H-mmh Human Bound (RU) Aa k¿ (l / s) á'd lVEi tU 1 (min) (1 / Ms) H4HH683N 49 81 5.48Et05 1.47E-03 2.69 E-09 8 1 H4H12171P 59 ~ 80 5.92ΕΙ0Ϊ' 9.63E-04 1.63E-09 12 i .. .......__ H4H12161P 41 54 1.18E-05 9.25E-04 7.84E-09 Η4ΙΠ2176Ρ2 45 69 2.57E-05 9.58E-04 3.73E-09 12 H4H12163P 60 85 7.24E¿05 2.90E-03 4.00E-09 4 H4H12167P 38 65 8.81 E+05 2.57E-03 2.91E-09 5 II4H121 75P 25 30 1.37E + 05 9.50E-03 6.94E-08 1 H4H12159P 51 82 6.38E4 05 9.48E-04 1.49E-09 12 H4H12164P 59 68 1.95E+05 1.06E-03 5.46E-09 11 H4H12168P 34 29 2.43EI04 1.23E- 03 5.04E-08 9 H4H12169P 61 1 79 4.29EI05 7.39E-04 1.72E-09 16 H4H11686N 40 74 4.19E+05 8.00E-04 1.91E-09 14 Η4ΙΠ2Ϊ70Ρ 36 ' 64 “5.59Ε+0Γ' 8.39E- 04 1.50E-09 14 H4H12177P2 45 51 ' 2.76E-05 2.76E-03 ” 1.00E-O8 ' ~ 4 H4H12183P2 33 t 36 9.58Ε-Ό4 7.12E-04 7.43E-09 16 H4H12166P 7 1 58 6.24E-05 1.31E-03 2.O9E-09 9 Comparator 1 41 5 NB NB NB NB Comparator 2 23 47 1 8.39El05 ____________ 1.05E-03 1.25E-09 l_.2L 147 Table 10. Binding kinetic parameters of anti-C5 monoclonal antibodies binding to human C5 R885C-mmh at 37°C. 07 / I ηη / Ρ7Π7 / Β / ν Antibody Quantity of 1 OOnM C5 Kd 4½ antibody R885C-mmh captured human (RU) bound (RU) (1 / Ms) ' (l / s) (M) (min) H4H11683X 48 78 4381-505 1.431503 3.25E-09 8 ' H4H12171P 59 78 4.77B - 05 9.57E-04 2.01E-09 12 H4H12161P 44 49 1.101505 9.01 E-04 8.171-509 13 H4H12176P2 44 55 'Ί.4Π505” 1.0 3E-03 7.321509 11 H4H12163P 59 8' 5.661505 2.811503 4.97 E-09 ' 4 ~ ΙΊ4Η12167Ρ 38 64 6.84E-05 2.491503 3.641509 5 H4H12175P 25 4 1.121505 1.791502 1.591507 1 H4H12159P ' 51 “ “ 68 5.61 1-505 9.75E-04 1.741x09 12 ' H41I12164P ” 64 1.77E Ό5 1.041503 5.851509 11 Η4Η12Ϊ68Ρ ~ 34 21 638E+04 5 691:-04 8.901509 20 II4II12169P 61 75 3.291x05 7.371504 2.241509 16 r H4H1Í686N ” ' 69 ' 2.841-505 7.91 E-04' 2.78 1-709 ' 15 ' H4H12170P 36 61 4.241505 8.701504 2.05E-09 13 H4H12177P2 43 31 1.071-5 05 5.071503 4.76E-08 2 H4H12183P2 5.12E04 9Ϊ97Ε-04 Í.95E-08 12 H4H12166P 72 54 4.91Ε-05 1.26E-0 3 2.56E-09 9 Comparator 1 ' 41 2 NB NB NB NB Comparator 2 23 42 7341-5 05 ' 1.071503 * 1.451509 L_______ ...m ... ........ 11 At 25°C, the 25 anti-C5 antibodies of the invention bound to human C5 with Kd values ​​ranging from 73 pM to 8.4 nM as shown in Table 3. At 37°C, the anti-C5 antibodies of the invention The invention bound to human C5 with Kd values ​​ranging from 103 pM to 18.5 nM as shown in Table 4. At 25°C, 25 of the 25 anti-C5 antibodies of the invention tested bound to C5-mmh of 148 monkey with Kd values ​​ranging from 133 pM to 64 nM as shown in Table 5. At 37 ° C, 25 of the 25 anti-C5 antibodies of the invention tested bound to monkey C5-mmh with values ​​ranging from 133 pM to 118 nM as shown in Table 6. At 25°C, 16 of the 16 anti-C5 antibodies of the invention tested bound to human C5 R885H-mmh with Kd values ​​range from 147 pM to 10.9 nM, as shown in Table 6. shown in Table 7. At 25°C, 16 of the 26 anti-C5 antibodies of the invention tested bound to human C5 R885Cmmh with Kd values ​​ranging from 251 ρΜ to 190 nM as shown in Table 8. At 37°C , 16 of the 16 anti-C5 antibodies of the invention tested bound to human C5 R885H-mmh with Kd values ​​ranging from 1.49 nM to 69.4 nM as shown in Table 9. At 25 ° C, 16 of the 16 anti-C5 antibodies of the invention tested C5 of the invention tested bound to human C5 R885C-mmh with Kd values ​​varying from 1.7 4 nM to 159 nM as shown in Table 10. Example 4. Antibody binding to C5 across different pHs The effect of pH on the dissociation rate of recombinant human C5 bound to purified anti-C5 monoclonal antibodies was determined using a real-time surface plasmon resonance biosensor using a Biacore T200 instrument. The Biacore sensor surface was first derived by amine coupling with a mouse monoclonal anti-human Fc antibody (GE, #BR-1008-39) to capture antibodies. 149 monoclonals: anti-C5 expressed with human IgG4 Fe. All Biacore binding studies were carried out using two PBS-T running buffers, pH 7.4 (0.01M NazHFCVNaHzFO / i, 0.15 M NaCl, 0.05% v / v Tween-20, adjusted to pH 7.4) and PBS-T, pH 6.0 (0.01M Na:HPC / NaH2PO4, 0.15M NaCl, 0.05% v / v Tween-20 , adjusted to pH 6.0). Different concentrations of human C5 (EMD, catalog number 204888) or monkey C5.mmh (prepared in PBS-T, pH 7.4 from running tarpan (ranging from 100 nM to 11.11 nM, threefold dilutions) were injected onto the surface captured with anti-C5 monoclonal antibody for 3 minutes at a flow rate of 50 pL / minute and its dissociation in two running buffers PBST, pH 7.4 and PBS-T, pH 6.0 was monitored for 6 minutes. All kinetic experiments Binding tests were carried out at 25° C and 37° C. The kinetic dissociation constant (La) was determined by fitting the real-time detection sensors to a 1:1 binding model using Scrubber 2.0 curve fitting software. c. The dissociative binding half-lives (tb) were calculated from kd as: Jn(2L .½ (min) = 60*kd The half-life relationships for the binding of human C5 to different anti-C5 monoclonal antibodies at 25 °C and 37 °C in 150 two operating lamps PBS-T, pH 7.4 and PBS-T, pH 6.0 are shown in Tables 11 and 12. Table 11. Half-life ratios of selected anti-C5 antibodies to human C5 at 25°C. Captured ti / 2 mAB ratio >— ... pH7.4 / pH6.0 ------- ----- --------- H4II12169P IC H4H12176P2 IC H4H12161P IC II4II12159P < 0.3 — H4H12170P < 0.5 H4H12166P 4.5 --- _ ------ __ — . H4H12183P2 IC — H4H12167P 0.6 -------------- H4H12164P 0.3 H4H12163P 1.2 ------------ ------------- H4H12175P 0.9 — ----- ------ 1141112177P2 <0.5 — - — H4H12171P 0.6 - -..... — H4H12168P 1.5 — ---- ... ----- ------- --- . . - H4H12166P2 9.3 — H4H12166P3 7.9 H4H12166P4 7.8 -... — H4H12166P5 8.3 .. . . —. . — _ — H4U12166P6 7.8 — — H4H12166P7 35 -- -------- ------- . . H4H12166P8 47 . ____ ---- .... II4I112166P9 31 H4H12166P1 0 33 - H4H11683N 2 H4H11686N 2 I IC = Inconclusive 151 Table 12. Half-life ratios of selected anti-C5 antibodies to human C5 at 37°C. 07 / I ηη / Ρ7Π7 / Β / νΐ captured inAB Ratio ti / 2 pH7.4 / pH6.0 H4H12169P IC H4H12176P2 < 0.4 H4II12161P < 0.7 H4H12159P < 0.2 H4H12170P < 0.2 H4H12166P 3.8 H4H12183P2 IC 1141I12167P 0. 2 Π4Ι112164Ρ <0.1 H4H12I63P 0.8 H4H12175P 0.9 II4H12177P2 1.3 H4H12171P 3.7 H4H12168P 1 H4H12166P2 7.3 H4H12166P3 6.6 ΙΙ4ΙΙ12166Ρ4 7.6 H4H12166P5 7.6 H4H12166P6 8.2 H4H12166P7 21 H4H12166P8 36 H4H12166P9 28 H4H12166P10 19 H4H11683N 1.4 H4H11686 N 0.8 conclusive IC = No Half-life relationships for the binding of monkey C5 to different anti-C5 monoclonal antibodies at 25 °C and 3 / °C 152 in two PBS-T operating lamps, pH 7.4 and PBS 6.0 are shown in Tables 13 and 14. Table 13. Half-life ratios of selected C5 antibodies to monkey C5 at 25°C. T, pH anti- Ratio ti / 2 captured mAb pH7.4 / pH6.0 H4II12169P 3.4 H4H12176P2 > 9.1 H4H12161P Ib H4H12159P 1.2 H4H12170P > 1.7 H4H12166P 18.5 H4H12183P2 5.8 H4H12167P 9. 2 H4H12164P 2.9 ΓΙ4Η12163Ρ 9.7 H4H12175P 3.6 H4H12177P2 3.7 H4H12171P 2.1 , H4H12168P 3.8 H4H1 1683N 0.34 H4H11686N I 0.37 IC = Inconclusive Table 14. Half-life ratios of anti-C5 antibodies selected for monkey C5 at 37°C. 153 I mAb captured! ratio ti / 2 | I pII7.4 / pII6.0 H4H12169P 2 II4H12176P2 2.8 U4H12161P 10.7 II4II12159P 6.3 H4H12170P 4.7 H4H12166P 7.1 H4H12183P2 2.4 H4H12167P 4.4 II41I12164P 1.1 H4H12 163P 3.3 ΙΙ4Π12175Ρ 0.4 H4H12177P2 , 1.5 — .. . ....! H4H12171P 4.7 H4H12168P I 4 H4H11683N i 0.7 H4H11686N 0.5 IC = Inconclusive As shown in Tables 11-14, selected anti5C5 antibodies showed pH-dependent binding, as seen by tb ratios. Example 5. Cross-octet competition between anti-C5 antibodies Binding competition between anti-C5 monoclonal antibodies (mAbs) was determined using a real-time label-free bio-layer interferometry assay on an Octet RED384 biosensor (Pall ForteBio Corp.). The entire experiment was carried out at 25°C in 0.01 M HEPES pH 7.4, 154 0.15Μ NaCl, 0.05% v / v Tween-20 surfactant, 0.1 mg / ml BSA (HBS-P Octet Lamp) with the plate shaking at a speed of 1,000 rpm. To evaluate whether 2 antibodies were able to compete with each other to bind their respective epitopes on a human C5 (hC5 purified from plasma, EMD), about 1.5 nm of anti-human C5 mAb was captured for the first time in the Octet biosensor tips coated with anti-hFc antibody (Pall ForteBio Corp., #18-5060) by immersing the tips for 3 minutes in wells containing a solution of 50 pg / mL of anti-human mAb C5 (later named mAbl). The biosensor tips captured with the antibody were then saturated with a blocking H4H isotype control mAb (later named blocking mAb) by immersion in wells containing 200 pg / mL of blocking mAb solution for 4 minutes. The biosensor tips were subsequently immersed in wells containing a co-complex solution of 50 nM hC5 and 1 pM of a second anti-human C5 mAb (later designated mAb2), which had been preincubated for 2 hours, for 4 minutes. The biosensor tips were washed in OcLeL HBS-P Lamp between each step of the experiment. The real-time binding response was monitored during the course of the experiment and the binding response at the end of each step was recorded. The 155 binding response of rnAbsf pre-complexed in human C5 to mAbl was corrected for background binding, compared and the competitive / non-competitive behavior of different anti-C5 monoclonal antibodies determined. Table 15 explicitly defines the ratios of antibodies competing in both directions, regardless of binding order. Table 15. Cross-competition between pairs of selected anti-C5 antibodies. First mAb (mABl) captured using AHC Biosensors Octet mAb2 antibodies shown to compete with mAbl II4II12183P2 H4H12167P; 1I4H12166P; II4H12163P II4II12167P II41112183P2; 1141112166P; II4II12163P H4II12166P II4II12183P2:1I4II12167P; H4H12163P Π4Η12163Ρ II4II12183P2; II41I12167P; 1141112166P H4H12159P - ----- - - U4H12169P; H4H1 1683N; H41112170P II4II12169P II41I12159P; II4II11683N; I14II12170P II4II1 1683N II4II12159P; H4II12169P; I14H12170P H4H12170P Η41Π2159P; H4H12169P; 1141111683N H4H12175P I14H12177P2 II4II12177P2 II4H12175P H4HI2176P2 H4H12164P H4II12164P II41I12176P2 H4H12168P none II4II12161P none H4H11686N none 156 Example 6. Inhibition of C5-mediated complement-dependent cytotoxicity in a B cell bioassay. This Example describes a bioassay to test the role of C5 using an anti-CD20 antibody in the classical complement pathway. Therapeutic antiCD20 antibodies against the B cell-specific cell surface antigen CD20 have been shown to drive the CDC of B cells (Glennie et al., 2007, Mol. Immunol. 4 4:3823-3837) and the CDC assay using Cell lines expressing CD20 have been described previously (Flieger et al., 2000, Cell. Immunol. 204: 55-63). Daudi cells, a human B cell line expressing CD20, complement-preserved serum or C5-depleted serum with exogenous C5 variants, and an anti-CD20 antibody (antibody comprising Vh / Vl of 2F2 from US Patent 8,52 9,902) were used. ) to evaluate the role of C5 activity in CDC. For the CDC C5 bioassay, Daudi cells were seeded in 96-well assay plates at 10,000 cells / well in RPMI containing 10% FBS, penicillin / streptomycin, Lglutamine, sodium pyruvate and non-essential amino acids (RPMI Complete Media). or RPMI containing 1% BSA, penicillin / streptomycin and L-glutamine (RPMI / BSA). All trials that tested mutated anti-hC5 antibodies, along with non-mutated antibody trials with C5 containing Q7J I ηη / Ρ7Π7 / Β / ν 157 human sera were tested in complete RPMI medium, while assays testing unmutated antibodies with African green monkey serum and human C5 variant were tested in RPMI / BSA medium. To measure CDC with human or monkey serum, anti-CD20 antibody was diluted 1:3 from 100 nM to 2 pM (including a control sample containing no antibody) and incubated with cells for 10 minutes at 25°C followed by the addition of 1.66% serum or 1.66% C5-depleted serum and 6.6 nM C5 variant proteins. The amount of C5 protein to be added to C5 depleted serum was based on the reported value of C5 concentration in human serum of 0.37 uM (Rawal et al 2008, J. Biol. Chem. 283: 7853-7863). To test inhibition of CDC by C5 antibodies, C5 antibodies were diluted 1:3 from 100 nM to 2 ρΜ (including a control sample containing no antibody) and incubated with 1.66% serum or 1.66% C5 depleted serum. and 6.6 nM of C5 variant protein for 30 minutes. Ten minutes before the addition of serum antibodies to the cells, anti-CD20 antibody was added to the cells at 1 nM, 2 nM, 3 nM, 3.5 nM, 7 nM, 10 nM, or 30 nM. At the end of the incubation with the anti-CD20 antibody, the antibody / serum mixture was added to the cells. Cytotoxicity was measured after 3.5 hours of incubation at 37 °C and in 5% COz, followed by 15 minutes of incubation at 158 25°C, and the addition of CytoTox-Glo™ reagent (Promega, #G9292). CytoTox-Glo™ is a luminescence-based reagent that measures cell destruction, such that greater luminescence is observed with greater cytotoxicity (measured in relative light units, RLU). Untreated cells in control wells were treated with digitonin immediately after addition of CytoTox-Glo™ reagent to determine maximal cell killing. Plates were read for luminescence with a Victor X instrument (Perkin Elmer) 15 minutes after addition of CytoToxGlo™. When calculated, percent cytotoxicity was calculated with RLU values ​​using the following equation: (Experimental Cell Lysis - Background Cell Lysis) % Cytotoxicity = lOOx. (Maximum Cell Lysis - Background Cell Lysis) In this equation, background cell lysis is the luminescence of cells treated with media and serum alone without any anti-CD20 antibody and maximum cell lysis is the luminescence of cells treated with digitonin. The results, expressed as % cytotoxicity or RLU, were analyzed using non-linear regression (4-parameter logistic) with Prism 5 software (GraphPad) to obtain ECso and IC50 values. The inhibition of 159 antibodies was calculated so that 0 -100% inhibition is the range of inhibition from the concentration of the anti-CD20 antibody in the assay without inhibitor to 0 nM of the anti-CD20 antibody. Results A total of 25 anti-human C5 antibodies, 16 non-mutated and 9 mutated, were tested for their ability to inhibit C5 in the CDC assay using Daudi cells with an anti-CD20 antibody and with either human sera (with normal hC5 or C5 variants) or African green monkey sera. Various residues in the complementary determining regions (CDR) of H4H12166P were changed to histidines to generate 9 mutated antibodies, H4H12166P2H4H12166P10. Histidine mutations in CDR have been shown to confer pH dependence on target antigen binding leading to improved pharmacokinetics (Igawa et al., 2010, Nat. Biotechnol. 28:1203-1202). Table 16. Inhibition of non-mutated CDC anti-hC5 antibody with 1.66% serum and anti-CD20 antibody in cells Q7J i nn / C7nz / B / Y Daudi 160 Serum Human Human African green monkey C5 depleted Human and 6.6nM Variant C5 R885H C5 depleted HUMAN and 6.611M Variant C5 R885C EC50 [M] of anti-CD20 antibody (with 1.66% serum) 1.0E-09 1.4E-09 2.4 E -09 1.9E-09 2.7E-09 Constant anti-CD20 antibody (with 1.66% InM 3nM 3.5nM 30nM serum) Antibody IC50| M| IC50[M] (Maximum % IC50[M] IC50 [M] Maximum % Inhibition)* Inhibition)* Η4ΗΠ683Ν Not Tested L2E-09 4.0E-09 1.3E-O9 9.0E-10 Η4Π11686.Ν Not Tested 1.5Ε- 09 4.4 E-09 1.1E-09 4.5E-I0 H4H12159P 3.2E-09 Not Tested 3.4E-09 l .4E-09 1.0E-09 H4II12161P 2.4E-09 Not Tested 2.6E-09 E8E-09 1.0E- 09 U4H12163P 3.4E-09 Not Tested 3.7E-09 2.1 E-09 1.8E-09 1.1 E-09 Η4Π12164Ρ 2.4F.-09 Not Tested 5.8E-09 8.2E-10 ΙΙ4ΙΠ2166Ρ 2.6E-09 1 Not Tested ado 4.5E -09 1.3 E-09 4.6Ε-Ϊ0 H4H12167P 2.5E-09 Not Tested 3.5E-09 1.9E-09 1.0E-09 H4H12168P 1.5E-09 Not Tested 2.0E-09 2.3 E-09 8.6E-10 H4H12169P 1.7 E-09 Not Tested 2.9E-09 1.3 E-09 6.7E-10 H4II12170P 2.0E-09 Not Tested 3.7E-09 4.8E-10 4.3E-10 Γ H4H12171P 1.9E-09 Not Tested 3.3E-09 1.6E -09 6.5E-10 H4H12175P 2.2E-09 Not Tested 5.2E-09 4.2E-09 >2.0E-08 (67%) H4II12176P2 2.7E-09 Not Tested 3.5E-09 2.1 E-09 1.3 E-09 H4H12177P2 2.2E-09 Not Tested 6 1E-09 2.4E-09 1.6E-09 II4H12183P2 1.7E-09 Not Tested 1.4E-08 1.2E-09 4.5E-10 Comparator 1 2.3E-09 1.8E-09 >9.0E -08 (49%) No inhibition No inhibition Control mAb 1 No inhibition No inhibition Not Tested Not Tested Not Tested Control mAb 2 Not Tested Not Tested No inhibition Sm udubition No udtibition Unless otherwise indicated, t or d to inhibition is -100%. As shown in the Tables and 17, anti-hC5 antibodies showed complete inhibition of C5-mediated CDC present in 1.66% of human serum. The IC50s of the unmutated antibodies ranged from 1.2 to 3.4 nM. The IC50 of the mutated antibodies ranged from 3.0 nM to 12 nM. The non-mutated parental H4H12166P antibody gave complete inhibition with IC50 of 2.6 nM and 2.9 nM. 07 / I ηη / Ρ7Π7 / Β / ν 161 Table 17. Inhibition of the mutated anti-hC5 antibody of CDC with 1.66% serum and anti-CD20 antibody in cells Daudi Serum Human African Green Monkey C5 depleted Human and 6.611M λ-7aliante C5 R885H C5 depleted Human and 6.6nM Variant C5 R885C EC50 [M] of anti- 1.9E-09 2.6E-09 6.3E-09 9.5E-09 CD20 antibody (with 1.66% serum) Anti-CD20 antibody constant 2nM lOnM 7nM 30 π M (with 1.66% serum) Antibody ... . IC50 [M] (% IC50[M] Maximum of IC50[M] IC50[M| inhibition)* H4H12166P 2.9E-09 5.6E-09 1.3E-09 7.6E-10 II4H12166P2 3.7E-09 9.7E-09 1.7 E-09 1.2E-09 H4H12166P3 7.8E-09 >3.0E-08 (64%) 2.9E-09 1.7E-09 H4H12166P4 3.5E-09 7.9E-09 Ϊ.5Ε-09 9.6E-10 H4H12166P5 4.9E -09 >3.0E-08 (75%) 2.1E-09 1.4E-09 H4H12166P6 3.0E-09 9.9E-09 1.3E-09 7.9E-10 H4H12166P7 7.3E-09 >6.0E-08 (61%) 4.2E-09 2.3E-09 H4H12166P8 4.1E-09 >2.0E-08 (79%) 2.1E-09 1.2E-09 H4H12166P9 3.9E-09 >1.0E-08 (85%) 1.7E-09 7.7E -10 ΙΙ4Π12166Ρ10 1.2E-08 >1.0E-07 (34%) 7.0E-09 3.5E-09 Comparator 1 2.7E-09 >1.0E-07(35%) No inhibition No inhibition Control mAb 2 No inhibition No inhibition No inhibition No inhibition Unless otherwise noted, all inhibition is -100%. All sixteen unmutated anti-hC5 antibodies showed complete inhibition of CDC mediation by African green monkey C5 with IC50 ranging from 2.0 nM and 14 nM. Four of the 9 mutated antibodies showed complete inhibition of African green monkey-mediated CDC C5 with IC50 varying from 7.1 nM to 9.9 nM. The remaining six mutated antibodies were blocking with IC50 greater than 10 162 nM, and the maximum inhibition (on the lOOnM antibody) ranged from 34% to 85%. The unmutated parental antibody H4H12166P gave complete inhibition with IC50 of 4.5 nM and 5.6 nM. To test whether anti-hC5 antibodies inhibit the human C5 variants, R885H and R885C, C5-depleted human serum was tested with 6.6 nM of each C5 variant. All 25 anoi-hC5 antibodies showed complete inhibition of CDC mediated by the C5 R885H variant, with IC50s of the non-mutated antibodies varying in a range from 0.48 nM to 4.2 nM, while the IC50s of the mutated antibodies varied from 1.3 nM at 7.0 nM. The unmutated parental antibody H4H12166P gave complete inhibition with IC50 of 1.3 nM and 1.3 nM. Fifteen of the 16 wild-type anti-hC5 antibodies showed complete inhibition of CDC mediated by the C5 R885C variant with IC50 ranging from 0.43 nM to 1.6 nM. A wild-type antibody showed weak inhibition of CDC with a maximum inhibition of 67% (a 100 nM antibody) and an IC50 > 20 nM. All nine mutated antibodies showed complete inhibition of CDC mediated by the C5 R885C variant with IC50 ranging from 0.77 nM to 3.5 nM. The parental, unmutated antibody H4H12166P gave complete inhibition with an IC50 of 0.4 6 nM and 0.7 6 nM. Anti-CD20 antibody showed CDC of Daudi cells with 163 1.66% serum with EC50 of 1.0 nM, 1.4 nM, and 1.9 nM for human serum, 2.4 nM and 2.6 nM for African green monkey serum, 1.9 nM and 6.3 nM for hC5-depleted serum with the R885H variant of hC5, and 2.7 nM and 9.5 nM for hC5-depleted serum with the R885C variant of hC5. None of the irrelevant IgG control antibodies, Control mAbl and Control mAb2, demonstrated any inhibition of CDC. Example 7: Inhibition of C5a Activity as Determined by Luciferase Assay This Example describes an assay to test the activation of C5a through one of its receptors, C5aRl. C5aRl is a G protein-coupled receptor (GPCR) and can initiate several GPCR-coupled signaling pathways (Monk ct al. 2007, Br. J. Pharmacol. 152: 429-448). A bioassay was established using HEK293 cells stably transfected with human CSaRl (accession no. NP_001727.1) and human Gal6 (accession no. NP_002059.3) together with a luciferase reporter [NFAT response element (4X)- luciferase]. Gal 6 is a relatively promiscuous G protein that can couple to different types of GPCRs leading to the activation of PLC-β and subsequent elevation of Ca++, which in turn activates the transcription of the Pharmacol reporter gene. Sci. 26: 595-602). translocation of NFAT and the resulting (Kostenis et al. 2005, Trends The cell line- 164 ΗΕΚ293 / hGal6 / hC5aRl / NFAT-luc, was isolated and maintained in 10% DMEM containing 10% FBS, NEAA, pencilin / streptomycin, 500 gg / mL G418, 100 gg / mL hygromycin B and 7 gg / mL blasticidin. For C5a luciferase bioassay, HEK293 / hGal6 / hC5aRl / NFAT-luc cells were plated in 96-well assay plates at 20,000 cells / well in OPTIMEM (Invitrogen, #31985-070) supplemented with 0.5% BSA, penicillin / streptomycin and L-glutamine, and then incubated at 37°C and 5% CO2 overnight. BSA was used instead of FBS, as serum has been shown to cleave and inactivate hC5a (Klos et al., 2013, Pharmacol. Rev. 65: 500-543). The next morning, hC5a was titrated from 100 nM to 2 pM (including a control sample containing no hC5a) and added to the cells to determine the dose response titration curve for the cell line. To test hC5a antibody inhibition of hC5a, 500 pM hC5a was added to the cells. Immediately afterwards, antibodies diluted 1:3 from 100 nM to 2 pM (including a control sample containing no antibody) were added to the cells. The cells were incubated for 5.5 hours at 37°C in the presence of 5% CO2. Luciferase activity was detected after incubation with OneGlo™ reagent (Promega, 165 #Ε6051). OneGlo™ is a luminescence-based reagent that measures the amount of luciferase present in cells. In this assay, increased hC5a activation leads to increased luciferase production and luminescence (measured in relative light units, RLU). Luminescence measurement was performed with a Victor X instrument (Perkin Elmer). The results were analyzed by non-linear regression (4-parameter logistic) with Prism 5 software (GraphPad) to obtain ECso & IC50 values. The inhibition of the antibodies was calculated such that 0 to 100% inhibition is the inhibition range of hcóa 500 ρΜ without inhibitor at 0 nM hC5a. Four anti-hC5 antibodies were tested for their ability to inhibit hC5a activation of its receptor, hC5aRl, by measuring the degree of inhibition of hc5a activation of 500 pM HEK2 93 / hGal6 / hC5 aRl / NFAT-1uc cells. Table 18. Anti-hC5 antibody inhibition of 500 pM hC5a in HEK293 / hGal6 / hC5aRl / NFAT-luc cells EC?0[M] hC5a _ j__ mAb PID or REGN # v ।--------. ------------- A- Γ H2aM11682N ' H2aMl Í684N / H2aM11694N H2aM11695N Control mAb _______3.9E-10 Inhibition of hC5a 500pM Yc50[me 4.6E-10 3.5E-11 1.4E-1Ü 4.2E-11' No inhibition 166 As shown in Table 18, the four antibodies of the invention showed complete inhibition of 500 pM hC5a with IC50 ranging from 0.035 nM to 0.4 6 nM. An irrelevant IgG control antibody, Control mAb3, did not demonstrate any inhibition of hC5a. hC5a activated HEK293 / hGul6 / hC5aRl / NFAT-luc cells with an EC50 of 0.39 nM. Example 8. Hemolysis bioassay Classical pathway hemolysis (CH) assay and alternative pathway hemolysis (AH) assay were developed to test the antibody activity. CH is a selection assay for the activation of the classical complement pathway, which is sensitive to the decrease, absence and / or inactivity of any component of the pathway. CH tests the ability of serum complement components of the classical pathway to lyse sheep red blood cells (SRBC) pre-coated with anti-sheep antibody from rabbit red blood cells (hemolysin). When antibody-coated SRBCs are incubated with test serum, the classical complement pathway is activated and hemolysis occurs. If a complement component is absent, the CH level will be zero; If one or more components of the classical pathway decrease, the CH will decrease. (Nilsson et al 1984, J. Immunol. Meth. 72: 49-59). This assay is used for the characterization and selection of anti-C5 antibodies. 167 high affinity humans. Methods (A) Classical pathway complement hemolysis assay The desired number of sheep red blood cells (SRBC) were washed in GVB++ buffer and resuspended at 1χ10Λ9 cells / ml. To sensitize SRBCs, they were mixed with the same volume of rabbit anti-sheep hemolysin diluted 1:50 (1.5 mg / ml) at 37°C for 20 minutes. Sensitized SRBC cells were diluted to 2χ10Λ8 cells / ml in GVB++ before use in the hemolysis assay. Normal human serum or cynomolgus monkey serum was diluted to 2% or 10% in GVB++ buffer. To test the inhibition of C5-mediated hemolysis activity, test antibodies were preincubated for 20 minutes at 4°C, at concentrations ranging between 0.6 nM and 800 nM in 2% - 10% normal human serum or 10% of cynomolgous monkey or African green monkey serum. Round-bottom 96-well plates were used to measure hemolysis activity. A total of 100 μl of sensitized sheep RBC (2χ10Ά8 cells / ml) was plated in 96-well plates, followed by the addition of 100 μl of respective serum samples that was pre-incubated with the test antibodies. The cells were gently mixed and incubated at 37°C for 60 minutes. After the incubation time, the cells were centrifuged by 168 centrifugation at 1250xg at 4°C. A total of 100 ml of the supernatant was transferred to a new 96-well flat-bottom plate and read at 412 nm in the Spectramax microplate reader. Hemolytic activity was calculated at a final serum concentration of 1-5% for the treatments. The percentage of hemolysis was calculated as follows: Experimental Cell Lysis - Background Cell Lysis % Hemolysis = 1 OOx ------------------------------------- -------------------= Maximum Cell Lysis - Background Cell Lysis In this equation the background cell lysis is the OD at A412nm of cells incubated in GVB++ buffer containing no serum. Maximum cell lysis is the OD at A412nm of water-treated cells. The results, expressed as % hemolysis, were analyzed using nonlinear regression (4-parameter logistic; with Prism 5 software (GraphPad) to obtain IC50 values. Data represented as mean ± standard error of mean. (B) Alternative complement assay The desired number of rabbit red blood cells (RbRBCs) were washed in GVB-Mg:+ / EGTA buffer and re-suspended at 2χ10Λ8 cells / ml. Normal human or cynomolgus monkey serum was diluted to 10% in GVB-Mg2+ / EGTA buffer. To test the inhibition of C5-mediated hemolysis activity, antibodies at concentrations ranging from 3 nM to 800 nM were pre-incubated for 20 minutes at 4°C in 169 5-10% normal human serum or cynomolgus monkey serum. Round-bottom 96-well plates were used to measure hemolysis activity. A total of 100 μΐ RbRBCs (2χ10Λ8 cells / ml) were plated in a 96-well plate followed by the addition of 100 μl of 10% human or cynomolgus monkey serum or African green monkey serum that was pre-incubated with the antibody. anti-C5. The cells were gently mixed and incubated at 37°C for 60 minutes. After the incubation time, the cells were centrifuged at 1250 x g at 4°C. A total of 100 ml of the supernatant was transferred to a 96-well flat-bottom plate and read at 412nm in the Spectramax microplate reader. Hemolytic activity was calculated at the final serum concentration of 5% serum. The percentage of hemolysis was calculated as follows: Experimental Cell Lysis - Background Cell Lysis % Hemolysis = 100x Maximum Cell Lysis - Background Cell Lysis In this equation the background cell lysis is the OD at A412nm of cells incubated in GVB-Mg / EGTA buffer containing no serum or no anti-C5 antibody. Maximum cell lysis is the OD at A412nm of water-treated cells. Inhibition by anti-C5 antibodies, IC50 values ​​were calculated using non-linear regression (4-parameter logistic) with Brism 6 software (GraphPad). 170 Results (A) Inhibition of hemolysis of human C5 A total of 25 anti-human C5 (hC5) antibodies, 16 non-mutated and 9 mutated, were tested for their ability to inhibit C5 from normal human serum (NHS) in the CH50 assay using sensitized sheep red blood cells (SRBC) and assay AH50 using rabbit red blood cells (RRBC). Table 19: Anti-hC5 Antibody Inhibition of CP and AP Activity in 1% or 5% Normal Human Serum (NHS) mAb PID CP Human AP Human CP Human AP Human IC50 [M] IC50 [M] % Max. Inhibition % Max. Inhibition H4H12183P2 5.88E-09 1.60E-07 99.9% 78.9% 1141112176P2 4.58E-09 1.65E-08 94.1% 69.9% H4I112168P 3.33E-09 2.85E-08 97.5% 66. 2% H4H11686N 3.09E-09 1.3OE-O8 97.4 % 76.2% H4H12167P 3.68E-09 1.55E-08 99.9% 64.8% H4H12161P 2.56E-09 2.55E-08 93.7% 56.1% H4H12163P 2.72E-09 2.05E-08 96.1% 66.0% H4H12166P 2.80E-09 2.60E- 08 95.0% 70.9% H4H11683N 2.54E-09 3.40E-08 98.1% 73.2% H4I112159P 2.50E-09 1.75E-08 97.9% 73.4% 1141112177P2 2.34E-09 1.70E-0 8 97.5% 71.0% II4H12170P 2.39E-09 1.80 E-08 98.2% 81.1% IJ4II12175P 2.36E-09 2.00E-08 98.0% 80.2% H4H12171P 2.33E-09 1.55E-08 94.9% 42.0% H4H12164P 2.10E-09 1.45E-08 9 5.9% 69.7% I14H12169P 2.36E- 09 2.00E-08 98.3% 44.5% Isotype control No activity No activity No activity No activity 10 1_ As shown in Table 19, sixteen antihC5 antibodies of this invention showed more than 94% inhibition of hemolysis in the classical pathway (CP) mediated by C5 present in 171 1% human serum. The IC50 of the antibodies ranged from 2.1 to 5.9 nM and the percentage of inhibition ranged from 95% - 99%. All 16 anti-C5 antibodies showed more than 60% inhibition (except H4H12169P) in the alternative pathway (AP) hemolysis assay by C5 present in 5% NHS. The IC50s of the antibodies ranged from 13 to 160 nM and the percent inhibition activity ranged from 44% to 81%. Table 20: Anti-hC5 antibody inhibition of CP and AP activity in 5% normal human serum (NHS). mAb PID CP Human AP Human IC50[M] CP Human % Max Inhibition AP Human % Max Inhibition IC50[M] H4II12166P 1.09E-08 2.09 E-08 99.4% 86.9% H4H12166P2 1.59IÍ-08 4.781:-08 98.2% 81.3% H4H12166P3 1.34E-08 6.00 E-08 95.9% 78.3% II4II12166P4 1.32E-08 3.17E-08 98.6% 77.0% H4H12166P5 1.491-008 6.55E-08 97.1% 77.7% H4H 12166P6 1,031-:-08 2,841-:-08 98.1 % 82.4% H4H12166P7 2.43E-08 1.56E-07 93.7% 83.2% H4H12166P8 I.41E-08 7.30E-08 95.7% 73.3% H4H12166P9 1.16E-08 5.35E-08 93.7% 72. 2% H4H12166P10 4.44E-08 No activity 74.0% No activity Control isotype No activity No activity No activity No activity As shown in Table 20, all 9 mutated antihC5 antibodies showed inhibition of C5-mediated CP and AP hemolysis activity present in 5% of human serum. In the CP hemolysis assay, the unmutated parental antibody H4H12166P showed more than 98% inhibition 172 with IC50 of 10.9 nM. Eight mutated anti-hC5 antibodies showed more than 90% inhibition with IC50 ranging from 10.3 nM to 24.3 nM. The anti-C5 mutant antibody 12166P10 showed a partial inhibition of 74%. In the AP hemolysis assay, the unmutated parental antibody H4H12166P showed more than 85% inhibition with IC50 of 20.9 nM. Mutated anzi-hC5 antibodies showed an inhibition range of 7 2-83% and IC50 antibodies ranged from 2 8 nM to 0.15 μιΜ. (B) Inhibition of monkey C5 hemolysis A total of 25 anti-human C5 (hC5) antibodies, 16 non-mutated and 9 mutated, were tested for their ability to inhibit C5 from cynomolgus monkeys and African green monkeys in the CH50 assay using sensitized sheep red blood cells (SRBC) and the ΛΗ50 assay using rabbit red blood cells (RRBC). Table 21: Anti-hC5 antibody inhibition of CP and AP activity in 5% normal African green monkey (AGM) sera 173 Serum AGM CP Serum AGM AP AGM CP AGM AP mAb PDD IC50 [M] IC50[M] % Maximum inhibition 0 0 Maximum inhibition U4H12183P2 No activity No activity No activity No activity H4I112176P2 3.04E-08 4.77E-08 91.0% 83.2 % H4H12168P 2.80E-08 2.25E-08 90.8% 88.2% H4H11686N 4.82E-08 1.63E-07) 49.3% 50.4% H4H12167P 6.95E-08 6,951: -08 90.5% 53.4% ​​........ H4H1216IP 3.1913-08 4.75E-08 78.9% 35.7% H4H12163P 6.90E-08 2.16E-07 83.2% 58.5% H4H12166P 1.30E-07 2.33E-07 81.0% 44.2% H4H1168 3N 2.92E-08 4.08E-08 81.1% 88.1 % H4H12159P 2.58E-08 2.70E-08 93.4% 93.5% II4II12177P2 1.80E-07 1.0113-07 80.6% 8.80% H4H12170P 2.54E-08 2.69E-08 94.9% 90.9% 114 1112175P 1.18E-07 9.85E-08 84.5% 17.4% H4H12171P No activity 2.33 E-08 17.8% 69.70% H4H12164P 2.47E-07 1.78E-07 85.8% 15.60% I14H12169P 3.44E-08 9.1513-08 43.3% 45.70% orno shows in the Table 21, anti-hC5 antibodies showed different levels of inhibition of CP or ΆΡ hemolysis activity in 5% Irican green monkey serum. In the CP assay, two of the 16 anti-hC5 antibodies showed no inhibition of hemolysis activity. Fourteen antibodies showed inhibition ranging between 43 - 94%, with IC50 varying from nM and 180nM. In the hemolysis test AP, thirteen of the 17 antibodies showed an inhibition activity varying between 1 / % 93% with IC50 varying from 22.5 nM to 233 nM. 174 Table 22: Inhibition of the anti-hC5 antibody of the CP and AP activity in 5% normal Cinomolgo (Cyno) monkey sera Serum CP Serum AP CP Cvno AP Cyno Cyno Cyno mAb PID IC50 [M] IC50 [M] % Maximum % Maximum inhibition inhibition 1I4H12183P2 1.42E-07 2.96E-08 64.6% 100.0% ΙΙ4ΙΙ12171Ρ 8.70E-09 7.20E-09 92.9% 98.8% H4II12170P 8.20E-09 7.00E-09 99.0% 99.2% H4H12159P 7.75E-09 7.05E-09 99.3% 99.6% II4H12168P 1.031x08 5.45E-09 99.0% 99.7% H 4H1 1683N 9.00E-09 7.15E-09 98.8 % 98.9% H4H12176P2 1.47E-08 7.70E-09 97.5% 99.3% ΙΙ4Π12161Ρ 2.79E-08 7.80E-09 100.0% 98.4% II4II12169P 1.991x08 7.95E-09 92. 8% 96.30% 1141111686N 1.411x08 9.00E-09 94.5% 98.7 % IÍ4H12163P 1.65E-08 1.021x08 96.4% 98.5% ___ H4H12167P 2.13E-08 7.601x09 100.0% 98.30% H4H12175P 1.09E-08 8.05E-09 96.7% 98.10% U 4H12166P 2.01E-08 8.85E-09 94.2% μ - 98.60% H4H12177P2 1.711x08 8.80E-09 94.90% 98.10% H4II12164P 1.961x08 9.10E-09 94.7% 98.70% Isotype control No activity No activity No activity No activity As shown in Table 22, anti-hC5 antibodies (except H4H12183F which showed 64% inhibition of CP) showed more than 90% inhibition of the CP or AP hemolysis assay in 5% Cinomolgo monkey serum. In the CP hemolysis assay, the IC50s of the antibodies ranged from 7.15 nM and 142 nM. In the hemolysis test AP, the IC50s of the antibodies ranged from 5.4 to 29.6 nM. 175 (C) Inhibition of human C5 hemolysis variant Selected anti-C5 antibodies were tested for their ability to inhibit the human C5 variant (see Example 3 herein) from human C5 serum depleted in the CH50 assay. In C5-depleted human serum supplemented with the exogenous C5 variant R885H, H4H12166P, and Comparator 2 blocked CP hemolysis with IC50 values ​​of 6.0 nM and 4.4 nM, respectively, and ICgo values ​​of 7.6 nM and 5.5 nM, respectively. For the R885C variant, H4H12166P and the Comparator 2 blocked CP hemolysis in C5-depleted human serum with exogenous C5 variants with an IC50 of 9.3 nM and 6.8 nM, respectively, and ICgo values ​​of 11 nM and 8.2 nM, respectively. As expected, Comparator 1 did not block the hemolytic activity of the human C5 variants. (D) Inhibition of human C5b-6 complex Selected anti-C5 antibodies were tested for their ability to inhibit the human C5b-6 complex from C5-depleted human serum in the CH50 assay. H4H12166P potently blocked CP hemolysis in C5-depleted human serum supplemented with exogenous huC5b-6 complex with an IC50 of 3.8 nM and an ICgo value of 5.8 nM. In contrast, Comparator 1 blocked C5b-6 complex-mediated hemolysis with lower potency, with values ​​of □7 / 1 nn / C7n7 / B / v 176 IC50 of 5.0 nM and an ICp.o value of 46 nM respectively. Comparator 1 inhibited only 70% of total hemolysis at the highest concentrations tested. Comparaoor 2 did not block the hemolytic activity of the human C5b-6 complex. Example 9: Generation of C5a anti-C5 antibody block in the CP hemolysis assay To evaluate whether anti-C5 antibodies inhibit C5a generation, supernatants from the classical pathway (CP) hemolysis assay were analyzed for C5a levels by ELISA. C5a, generated as a result of cleavage of C5, is a 74 amino acid protein fragment. C5a is rapidly metabolized by serum carboxypcpeptidases to a more stable and less active 73 amino acid form, C5a des-Arg, by removal of the C-terminal arginine. Quantification of C5a des-Arg therefore provides a reliable measurement to monitor C5a generation in vivo and in vitro. The MicroVue C5a ELISA kit used here detects C5a des-Arg according to the information provided by the manufacturer. Preliminary experiments (data not shown) indicate that the primary 74 □7 / 1 nn / C7n7 / B / v amino acid form of C5a is also detected. For the purposes of this Example, both 177 forms will be collectively referred to as C5a. C5a protein levels were determined in supernatants from the CP hemolysis assay using; complement-preserved normal human serum (NHS) pre-incubated with H4H12166P or isotype control antibody as described in Example 8. C5a protein levels were measured using the MicroVue C5a ELISA kit according to the manufacturer's instructions. Briefly, samples were diluted and incubated on plates precoated with capture antibody (mouse anti-C5a specific for a neo-epitope on human C5a). Human C5a protein provided by the manufacturer was used as a standard for calibration. C5a was detected in the supernatants using HRP-conjugated detection antibody (mouse monoclonal antibody to the C5a region of C5). The chromogenic HRP substrate, 3,3',5,5'-tetramethiIbenzidine (TMB), was added to detect HRP activity. A 1N hydrochloric acid solution was used to stop the reaction, and the optical density at 450 nm (OD450) was measured on a SpectraMax plate reader. Data were analyzed using nonlinear regression (4-parameter logistic) in GrapnPad Prism. The concentration of C5a was expressed as ng / ml of supernatant. In the assay using 5% NHS, H4H12166P blocked □7 / 1 nn / C7n7 / B / v 178 potently increases C5a protein levels in a dose-dependent manner with an IC50 of 8.5 nM, while the isotype control antibody had no effect on C5a levels (Figure 1). Maximum blocking at the highest H4H12166P concentration tested (267 nM) resulted in an approximately 10-fold decrease in C5a levels to 3.8 ng / mL (0.3 nM), compared to 34 ng / mL (2.8 nM) observed at the lowest concentration of H4H12166P tested (1 nM) in 5% serum. The C5a concentration observed for maximum blockade was close to the C5a background level of 2.3 ng / ml (0.2 nM) in 5% untreated NHS. Example 10: Characterization of the pharmacokinetics and pharmacodynamics of anti-C5 antibodies in cynomolgous monkeys This example describes the characterization of the pharmacokinetics (PK) and pharmacodynamics (PD) of selected anti-C5 antibodies performed in male cynomolgus monkeys. Endogenous C5 levels were determined before anti-C5 antibody dosing and were used to stratify the animal dose groups. Total circulating C5 levels in cynomolgous monkeys were determined using a Human Complement C5 ELISA (Abeam, cat # ak>125963), which was carried out as 179 according to the manufacturer's recommendations. The average concentrations of C5 protein in monkeys were determined as 90.85 gg / mL + 19.17 pg / mL. For each anti-C5 antibody, 4 cynomolgus monkeys were administered with a single intravenous (IV) injection at a dose of 15 mg / kg. Blood samples were collected from each animal from predose to 1680 hours (70 days), processed into serum, and frozen at −80°C until analyzed for PK and PD. Analysis of Total IgG Antibody Level by ELISA Immunoassay Total antibody concentrations in monkey serum samples were measured using a non-validated direct ELISA. The ELISA procedure used a microtiter plate coated with a monoclonal anti-mouse IgGl / IgGi Ec antibody. Different anti-C5 antibodies were added to the plate and the anti-C5 antibodies captured on the plate were detected using a biotinylated anti-mouse IgG4 Fe monoclonal antibody, followed by NeutrAvidin conjugated to horseradish peroxidase (NeutrAvidin HRP). A luminol-based substrate specific for peroxidase was then added to achieve a signal intensity that is proportional to the concentration of the total anti-C5 antibody. 07 / I ηη / Ρ7Π7 / Β / ν captured. The relative light unit (RLU) measurements of 180 calibration standards and their respective nominal concentrations were fitted using a weighted 4-parameter logistic equation to generate a calibration equation describing the anoi-C5 antibody concentration and assay response relationship. The lower limit of quantification (LLOQ) was 1.56 ng / ml in the assay (2% monkey serum) and 78 ng / ml in pure monkey serum. Determination of station parameters PK parameters were determined by non-compartmental analysis (NCA) using software Phoenix® WinNonlin® (Version 6.4, Cortara, LP) and an IV-bolus dosing model. All PK parameters were derived from the respective mean concentration values, including the maximum observed serum concentration (Cmax), the observed peak concentration time, tmax, and the estimated observed half-life (TV). For each antibody, the area under the concentration curve versus the time to last measurable concentration curve (AUCiast) and extrapolated from time zero to infinity (AUC) were determined using a linear trapezoidal rule with linear interpolation and uniform weighting. 181 EP analysis by ex vivo hemolysis assay The pharmacodynamics of the selected anti-C5 antibodies were analyzed using the classical ex vivo route and the alternative route hemolysis assays. Classical route hemolysis assay: Sheep red blood cells (SRBC) were washed in GVB++ buffer (Veronal gelatin buffer with CaC12 and MgC12) (Boston BioProducts) and re-suspended at 1χ10Λ9 cells / ml. To sensitize SRBCs, a total of 1x10A9 / mL SRBCs were mixed with the same volume of rabbit anti-sheep hemolysin diluted 1:50 (1.5 mg / mL) at 37°C for 20 minutes. Sensitized SRBC were diluted to 2x10Λ8 cells / mL in GVB++ Lamp before use in the hemolysis assay. Blood was collected from cynomolgus monkeys before dosing and at 5 minutes, 4 and 8 hours, and 1, 2, 3, 5, 7, 10, 14, 18, 21, 28, 35, 42, 49, 56, 63 and 70 days post-dose for PD analysis. The serum was prepared and frozen until further use. On the day of the assay, cynomolgus serum from the respective time points was diluted to 10% in Lampon GVB4—. Round-bottom 96-well plates were used to measure hemolysis activity. A Lofal of 100 μl of sensitized SRBC (2x10Λ8 cells / mL) were plated in 96-well plates at 37 °C, followed by the addition of 100 μl of 10% cynomolgus monkey serum from the respective time points. The SRBCs were mixed and incubated at 37 °C for 10 182 minutes. After the incubation time, the cells were centrifuged at 1250xg at 4°C. A total of 100 gL of the supernatant was transferred to a new 96 flat-bottom plate and read at 412nm on a Spectramax microplate reader. Hemolytic activity was calculated at a final serum concentration of 5%. The percentage of hemolysis was calculated with the absorbency values ​​using the following equation: Experimental Cell Lysis - Background Cell Lysis % Hemolysis = 1 OOx ~--Maximum Cell Lysis - Background Cell Lysis In this equation the background cell lysis is the OD at A412nm of the SRBCs incubated in GVB++ Lampon that does not contain serum. The maximum cell lysis is the OD at A412nm of SRBC treated with water. The results, expressed as % hemolysis, were analyzed using nonlinear regression (4-parameter logistic) with Prism 6 software (GraphPad) to obtain IC50 values. Data are represented as mean ± Standard Error of the Mean. Alternative Route Hemolysis Assay: The desired number of rabbit red blood cells (RbRBC) were washed in GVB Mg2+ / EGTA Lamp and resuspended in 2x10Λ8 cells / mL. Blood from cynomolgus monkeys was collected before dosing and at 5 minutes, 4 and 8 hours, and 1, 2, 3, 5, 7, 10, 14, 18, 21, 28, 35, 42 and 4 9 days later. of the dose for PD analysis. The serum was prepared and frozen until further use. Plates were used 183 round-bottom wells to measure hemolysis activity. A total of 100 μΐ RbRBCs (2xlOA8 cells / mL) were plated in a 96-well plate at 37 °C followed by the addition of 100 μL of 10% cynomolgus monkey serum from the respective time points listed above. The RbRBCs were mixed gently and incubated at 37°C for 60 minutes. After the incubation time, the cells were centrifuged at 1250xg at 4°C. A total of 100 μΐ of the supernatant was transferred to a new 96-well flat-bottom plate that was read at 412 nm on a Spectramax microplate reader. Hemolytic activity was calculated for a final serum concentration of 5% and expressed as a percentage of the total hemolysis of erythrocytes in water. The percentage of hemolysis was calculated as described above. Results Selected anti-C5 antibodies (listed in Table 1) were tested in initial experiments for prolonged pharmacokinetic profiles in cynomolgus monkeys and C5-humanized mice (described in Example 10). H4H12166P and H4H12161P were selected to have high affinity along with prolonged PK and used in subsequent experiments in this paper with Comparator 1 and Comparator 2. Cynomolgo monkeys were administered a single dose of 15 mg / kg IV bolus of H4H12166P, H4H12161P o Comparator 2. Se □7 / 1 nn / C7n7 / B / v 184 determined serum concentrations of total antibody and percentage of classical pathway (CP) hemolysis activity at 19 time points over a 70-day lifespan. Alternative pathway (AP) hemolysis was determined at 17 time points over a 50-day lifetime period. Table 23 summarizes the mean antibody concentrations for the 3 antibodies. Mean total antibody concentrations versus time profiles are shown in Figure 2. Mean ?K parameters are described in Table 24. Table 23: Mean serum total IgG concentrations after a single intravenous injection of 15 mg / kg of selected anti-C5 antibodies to male Cynomolgo monkeys Time Ab serum concentration (ug / niL) (hours post Mean ± SD dose) H4H12166P H4H12161P Comparator 2 0 4 BLQ BLQ BLQ 0.083 4 445 130 456 '.26.2 459 155.2 4 4 328 127 d 360 :28.2 363 143. 8 8 4 353 t29.9 316 :21.5 357 i 16.1 24 4 282 :43.6 276 :32.4 248 i 19.6 48 4 225 : 15.2 221 :21.5 212 1 19.3 72 4 180 :15.0 181 H7.2 196 136.2 120 4 194 :20.9 162 110.7 179 123.3 168 4 171 :29.9 132 i 17.0 157 i 18.4 240 4 157 :12.7 96.1 : 17.3 1 14 i 13.0 336 4 H 120 r 10-2 49.3 : i 8.7 67.9 : 25.8 432 4 105 : 13.9 24.6 :11.8 42.6 t 15.9 504 4 92.2 · 10.6 13.8:9.95 28.6 113.1 672 4 75.1 i 15.8 6.16 12.40 10.9 16.25 840 3 59.6 14.79 2.44 :0.85 4.45 )2.63 10 08 3 43.3 12.89 1.16 :0.52 2.17 i 1.58 1 176 3 30.6 H.42 0.57 : 0.25 1.29 11.16 1344 3 25.9 13.74 0.315 10.16 :).1 / ().08 0.492 :0.49 1512 3 18.2 12.41 0.270 -.0.27 1680 3 11.5 11.51 0.07910.07 0.123 :0.15 185 Time = er time. hours after single dose injection; SD = standard deviation; BLQ = Below Quantification Limit After IV bolus administration, the total IgG concentration-time profiles of H4H12166P, H4H12161P, and Comparator 2 were characterized by a brief initial distribution phase followed by single elimination phases throughout the lifespan. The maximum concentrations of H4H12166P, H4H12161P and Comparator 2 were highly comparable, as the corresponding Cmax / Dose values ​​between all antibodies were within 1.1-fold (29.7, 30.4 and 30.6 [(ug / mL) / (mg / kg) ], respectively) (Table 24). Table 24: Mean pharmacokinetic parameters of total serum IgG concentrations after a single intravenous injection of 15 mg / kg of selected anti-C5 antibodies for male cynomolgous monkeys 07 / I ηη / Ρ7Π7 / Β / ν 186 Η4Η12166Ρ | Η4Η12161Ρ J Comparator 2 Parameter 15 mg / kg IV (n = 4) Cmax (pg / mL) Cmax / Dose (pg / mL) / (mg / kg) Mean ~ 445 29.7 SD _ Mean SD .Mean__________SD 30.0 ' 456 26.2 459 55.2 2.00 ' 30.4 1.75 30.6 3.68 Co (pg / mL) .. ... (hours) 448 0.083 30.5 ¡ 458 26.6 461 55.6 0 ' 0.083 0 0.083 0 ACCiastday ' (pg / mL) 5080 ..... 1040 __ 2350 357 i 2810 470 69.3 i 157 23.8 187 1 31.3 i 356 2810 470 44.7 157 23.7 188 31.4 0.0143 0.270 ' 0.0111 0.228 ' 0.0425 4.85 1 44.0 4.34 45.3 3.06 1.43 ~ 5.50 2.45 | 5.91 1.13 = Number of animals; Cma·-: = AUClast / Dose day · (pg / mL) / (mg / kg) j ~____ AUCmfday *(pg / mL) 5550 ^WCmÓDoSlS _ day · (pg / mL) / (mg / kg)___, CL (mL / h / kg) 0.114 Vss(mlAg) 60.4 ti / 2(day) 15.6 IV = Intravenous; n maximum concentration; Co = initial concentration determined by extrapolation; tmax = Time to Cma;.:; AUC = area under the concentration-time curve; AUCiast = AUC calculated from time zero to the time of the last positive concentration; AUCinf = AUC from time zero extrapolated to infinity; CL = Total body clearance; Vsa= Volume of distribution in steady state; tV = half-life; SD = Standard deviation. Note: tma:-: expressed in nominal hours. Evaluation of the concentration-time profiles showed that H4H12166P demonstrated the slowest clearance with terminal antibody concentrations b 10 qg / mL through the day 71 study. The kinetics of H4H12161P and Comparator 187 2 was similar; both demonstrated faster elimination than H4H12166P, with mAb concentrations > 10 pg / mL until day 22 and 29, respectively. Therefore, the normalized dose exposures (AUCiast / Dose) indicated that H4H12166P had the highest exposure at 339 days* (pg / mL) / (mg / kg), while H4H12161P and Comparator 2 had approximately 2 times lower exposure, 157 and 187 days+(pg / mL) / (mg / kg), respectively, than that of H4H12166P. The antibody half-life (tA) calculated during the elimination phase ranged from 5.5 to 15.6 days across dose groups and was also correlated with exposure, as H4H12166P had the highest ti / 2 corresponding to 15.6 days, while H4H12161P and Comparator 2 had ti / z values ​​of 5.5 and 5.9 days, respectively. The pharmacological effects of anti-C5 antibodies from cynomolgous monkey serum samples were determined ex vivo by complementing hemolysis by the classical route of sensitized sheep red blood cells (SRBC) and hemolysis by the alternative route (AP) of red blood cells. rabbit (RbRBC). Inhibition of hemolytic activity was calculated for a final serum concentration of 5% and expressed as a percentage of total RBC hemolysis in □7 / 1 nn / C7n7 / B / v 188 Table summarizes the ex vivo activity of the 3 antibodies as determined by the mean percentage of 07 / I ηη / Ρ7Π7 / Β / ν hemolysis. Table 25: Percentage of Hemolysis Activity of the Ex Vivo Alternative and Classical Route of Selected Anti-C5 Antibodies Time (hours and Classic route % Hemolysis in serum Alternative route % Hemolysis in serum cynomolgus, 10 min Mean ±SEM cmomolgo, 60 min Mean ± SEM postdose) H4H12166P H4H12161 P Comparator 2 H4H12166P II4II12161P Comparator 2 0 4 91.34 = 7.6 Not tested 84.36 ± 20.28 73.44 N7.26 64.90 : 19.51 55.77 ±10.82 0.083 4 3.5 H.4 Not tested 6.6 ±6.5 5.53 11.98 5.90 13.92 3.83 :3.93 4 4 2.35 i 1.06 Not tested 3.16 ±2. 2 7.43 ±2.54 6.53 : 2.7 5.30 :2.80 8 4 1.55 ±0.21 Ί Not tested 1.25 10.21 3.53 10.91 4.70 *2.77 1.98 10.83 24 4 7.7 i 6.08 Not tested 4.55 ±2.05 13.40 ±2.77 4.68 H.89 4.65 12.35 48 4 2. 85 i 2.19 Not tested 2.6 ±0.7 5.53 +2.40 7.68 15.22 2.28 10.67 72 4 0.9 :0.42 Not tested 1.3 10.28 7.95 ±3.36 5.95 12.23 1.45 :0.33 120 4 1.75+0.07 Not tested 1.3+0.14 16.38 ±6.91 H 7.60 ±1.94 1.68 ±0.22 1 68 4 1.6 :1.13 Not tested 1.4 10.56 21.28 18.24 10.75 '2.27 2.15 ±0.19 240 r4 1 10.14 Not tested 3.7 12.83 19.18 ±10.20 13.53 ±7.17 14.20 .' 16.73 ! 336 4 2.55 '2.05 Not tested 37.85 15.3 21.10 17.55 50.58 ¡12.91 ' 65.60*26.04 ' 432 4 1.35 :0.91 Not tested 105.25 :3.3 15.20 ±10.86 ” 59.75 112.65 5 4.55 * 19.1 1 504 4 3.55+2.05 Not tested 107.1 :4.38 33.15 ±8.80 88.55 124.63 1 85.63 127.48 1 672 4 2.2 :0.56 Not tested 88.9+23.05 75.25 ±18.30 88.55 ±8.53 91.58.118.55 840 3 3.075 i 2.70 Not tested 105. 37 ±53.4 46.65 ±5.30 92.33 :5.16 91.85 :2.33 i 1008 3 15.5 -.26.6 Not tested 108.85 +2.35 58.60 +9.48 92.45 :6.27 92.30 :2.69 ; 1176 3 58.33 139.55 Not tested 113.85 ±2.62 72.95 ±5.87 104.90 13.5 101.90 ±0.42 ' 1344 3 71.55 :43.02 Not tested 110.311.98 Not tested Not tested Not tested 1512 3 91.375 1 29.7 Not tested 110.610.85 i Not tested 112.1510.5 ¡ Not tested Not tested Not tested 1680 3 112.22 14.06 Not tested Not tested Not tested Time Time in hours after injection of a single dose; SEM Standard Error of the Mean; BLQ = Below the limit of quantification; MC = Not calculated As shown in Table 25 and Figure 2, the effects PD were measured by complementary CP (10 minute incubation) until day 70. H4H12166P blocked more than 95% of the 189 CP hemolytic activity until day 35. The activity returned to maximum pre-study hemolysis levels at day 70. Comparator 2 blocked approximately 95% of CP hemolytic activity until day 10, and the activity quickly returned to maximum levels of hemolysis before the study on day 18. The effects of PE were also measured by complement AP pathway hemolysis assays (60 minute incubation) until day 49. As shown in Table 25 and Figures 3A-3B, H4H12166P blocked 80% of the activity. total AP hemolytic activity until day 18 and the activity returned to the maximum hemolysis level before the study at day 50. H4H1216P and Comparator 2 blocked 90% of the AP hemolytic activity until day 7, and the activity returned to maximum hemolysis levels before the study at day 21. Example 11: PK / PD characterization of anti-C5 antibodies in C5-humanized mice In this set of experiments, the pharmacokinetics and pharmacodynamics of selected anti-C5 antibodies were evaluated in mice humanized to express the human C5 protein using Velocigene® technology (Valenzuela et al 2003, Nat. Biotechnol. 21: 652-659). . Humanized mice were engineered to replace the □7 / 1 nn / C7n7 / B / v exon 190 to exon 41 of the marine C5 gene by exons 2-42 of the human C5 gene (described in Publication Application US 2015 / 0313194, incorporated herein in its entirety). Total circulating human C5 levels were determined using a complement C5 ELISA (Abeam, cat #abl25963), which was carried out according to the manufacturer's recommendations. Determination of total drug level in serum by ELISA Concentrations of circulating anti-C5 antibodies, both C5-bound and non-C5-bound, were determined by total human antibody analysis using ELISA. Briefly, a goat anti-human IgG polyclonal antibody was immobilized at 1 pg / ml in PBS in 96-well plates overnight; The plates were washed to remove unbound IgG and then blocked with 5% BSA. Serial dilutions of anti-C5 antibody containing serum samples (6 points) and reference standards (12 points) of the respective antibodies were transferred to human IgG-coated plates and incubated for one hour. Plate-bound anti-C5 antibodies were then detected using a goat anti-human IgG polyclonal antibody conjugated to horseradish peroxidase. The plates were developed with TMB substrate 07 / I ηη / Ρ7Π7 / Β / ν 191 according to the manufacturer's recommended protocol and the optical density (OD) signals were recorded at 450 nm using a Perkin Elmer Víctor X4 Multimode Píate Reader. Serum concentrations were calculated based on the reference standard calibration curve generated using GraphPad software. Determination of station parameters PK parameters were determined by non-compartmental analysis (NCA) using Phoeziix®WinNonlin® software (version 6.3, Certara, L.P.) and an extravascular dosing model. Using the respective average concentration values ​​for each antibody, all PK parameters, including the estimated observed half-life (tV), and the area under the concentration curve versus time to last mean concentration curve (AUCiast) were determined using a linear trapezoidal ruler with linear interpolation and uniform weighting. PD Analysis by Hemolysis Assay The pharmacodynamics of selected anti-C5 antibodies were determined using a classical pathway complement hemolysis assay. Sheep red blood cells (SRBC) (sheep blood in Alsevers solution) were released in GVB++ Lampon (Veronal Gelatin Lamp with CaC12 and MgC12) (Boston BioProducts) and re-suspended in 1x10^9 07 / I ηη / Ρ7Π7 / Β / ν 192 cells / mL. To sensitize, lxl0A9 / mL SRBC was mixed with the same volume of rabbit sheep hemolysin diluted 1:50 (1.5 mg / mL) at 37 °C for 20 minutes. Sensitized SRBC were diluted to 2x10a8 cells / mL in GVB++ before use in the hemolysis assay. Serum samples from pre-dosed animals or humanized C5 mice dosed with anti-C5 antibodies collected on days 10, 20, 30, 40 and 50 post-dose were diluted to 20% in GVB++ Lampon. A total of 100 μΐ of sensitized SRBC (2x10'8 cells / mL) were plated in 96-well round-bottom plates at 37°C followed by the addition of 100 μΐ of 20% serum that was supplemented with 160-180 pg / mL human complement protein 3 (huC3). The cells were mixed gently and incubated at 37°C for 1 hour. After incubation, cells were centrifuged at 1250xg at 4°C. A total of 100 μΐ of supernatant was transferred to a new 96-well flat-bottom plate and read at A412nm on a Spectramax microplate reader. The percentage of hemolysis was calculated with the absorbance values ​​using the following equation: Experimental Cell Lysis - Background Cell Lysis % Hemolysis = 1 OOx -................................... .......———= Maximum Cell Lysis - Background Cell Lysis In this equation, background cell lysis is the OD a A412nm of SRBC incubated in GVB++ lamp that does not contain 193 serum. The maximum cell lysis is the OD at A412nm of the SRBCs treated with water. The results, expressed as % hemolysis, were analyzed by nonlinear regression (4-parameter logistic) with Prism 6 software (GraphPad) to obtain IC50 values. Data represented as mean + (standard error of the mean). Experiment 1 In this experiment, the pharmacokinetics and pharmacodynamics of the exemplary antibody H4H12166P were evaluated in comparison with Comparator 1 and Comparator 2 in humanized C5 mice. Total circulating C5 levels were determined using a Human Complement C5 ELISA (Abeam, cat #abl25963), which was carried out according to the manufacturer's recommendations. The average concentrations of human C5 in the mice were determined as 39.73 pg / mL + 17.82 pg / mL. There was a difference between male (55.4 ± 1.7 gg / ml, n = 47) and female (24.7 + 0.6 gg / ml, n = 49) mice. Prior to antibody dosing, male and female humanized C5 mice were stratified according to human C5 levels that averaged 40 pg / mL. For each anti-C5 antibody, cohorts of twenty-two mice received a single dose of 15 mg / kg of H4H12166P, Comparator 1, and Comparator 2 by subcutaneous (s.c.) injection. All mice were bled before dosing and one day after dosing. 194 injection for PK analysis. Furthermore, on days 10, 20, 30, 40, and 50 after injection, groups of 4 or 5 mice from each cohort were sacrificed and terminal hemorrhages were removed for PK and PD analysis. Day 1 serum samples 5 were the mean of the entire cohort for all 22 mice. The blood was processed into serum and frozen at -80°C until analyzed. Total antibody concentrations were determined at 7 time points and percent hemolysis activity was determined at 6 time points over the 50-day life span. Total anti-C5 antibody concentrations are summarized in Table 26. Total mean antibody concentrations versus time profile are shown in Figure 4. Mean PK parameters are described in Table 27. Table 26: Mean serum total IgG concentrations after a single subcutaneous injection of 15 mg / kg anti-C5 antibodies in humanized C5 mice 07 / I ηη / Ρ7Π7 / Β / ν ' Time (day);BA serum concentration (ug'inL) Medium + SD H4II12166P Comparator 1 Comparator 2 1 22 178:22.7 229140.7 164124.1 10 4 83.7122.2 102122.9 44124.1 20 5 57.1 ±26.8 29131.3 11.4110.3 30 5 3 8.1-67.6 30.1134.2 3.613.2 40 4 11.915.0 0.410.4 0.5-0.4 50 4* 9.3112.2 0.3 m0.3 0.3^0.2 195 Time = Time in hours after injection of a single dose; Day = Study day; SD = standard deviation; SEM = standard error of the mean; ND = Not detected; NS = No sample. *For Comparator 2, day 50, 5 n = three due to the inability of a sample to be analyzed due to technical problems. Table 27: Station parameters □7 / 1 nn / eznz / b / v Parameter Units H4H12166P ¡ Comparator 1 Comparator - - Day 1 mAb concentration pg / mL 178 229 164 AUC|ast daypg / mL 2801 2708 1418 tl / 2 d 11.3 4.7 7.6 Cmax = Maximum concentration; AUC = area under the concentration-time curve; AUCiast = AUC calculated from time zero to the time of the last positive concentration; TV = estimated observed half-life. The mean concentration versus time profiles in the day show that the three antibodies, H4H12166P, Comparator 1 and Comparator 2 had comparable serum concentrations of 178, 229, and 164 pg / mL, respectively. Comparator 1 had a similar clearance profile to H4H12166P until day 30, but at days 40 and 50 showed a rapid increase in clearance compared to H4H12166P. On day 50, H4H12166P had a 196 mean serum antibody concentration of approximately 9 pg / mL, while Comparator 1 and Comparator 2 had a mean serum antibody concentration 30 times lower than 0.3 pg / mL. Comparator 2 showed the lowest exposure of the three antibodies tested, with an approximately 2-fold lower AUCiast (1408 pg-days / mL) compared to H4H12166P (2801 pg-days / mL) and Comparator 1 (2708 pg-days / mL). / mL). The pharmacological effects of anti C5 antibodies H4H12166P, Comparator 1 and Comparator 2 humanized mouse C5 serum samples supplemented with human C3 were measured at day 50 and were determined live by complement classical pathway (CP) hemolysis of sensitized SRBC. The mean percentage of hemolysis for each antibody. anti-C5 is summarized in Table 28 and the mean percentage of hemolysis versus time is shown in Figure 5. Table 28. Ex vivo classical pathway percentage hemolysis activity of human anti-C5 antibodies. Time Classic route % hemolysis in 10% mouse air, 60 (Day) min. Mean + SE1M H4H12166P Comparator 1 Comparator 2 I 22 NS NS NS i ίο 4 12.6±7.79 10.39±2.88 12.06±9.12 20 5 18,818.1 21.59±17.53 65.08±52.87 30 5 13.76Μ0.9 78.98140.3 91.67116.74 40 4 41.71 ±40.7 101.0914.01 68.99±42.47 50 4* 62.2±56.6 88.99±17.51 ​​105.14±4.07 197 Time = Time in hours after injection of a single dose; Day = Study day; SEN = standard error of the mean; ND = Not detected; NS = No sample. For Comparator 2, day 50, n = three due to the inability of a sample to be analyzed due to technical problems. H4H12166P, Comparator 1 and Comparator 2 inhibited terminal complement hemolytic activity that appeared to correlate with antibody exposures. H4H12166P blocked more than 85% of hemolytic activity until day 30 and the activity returned to baseline levels by day 50. Comparator 1 and Comparator 2 blocked approximately 80% of hemolytic activity until day 20 and day 10, respectively, and activity returned to baseline levels on day 30 for both. Experiment 2 In this experiment, the pharmacokinetics and pharmacodynamics of the anti-C5 antibodies H4H12166P, H4H12161P, Comparator 1 and an isotype control were evaluated in humanized C5 mice (mice homozygous for C5 expression in humans). Total circulating C5 levels were determined using a Human Complement C5 ELISA (Abcam, cat #ab 125963), which was carried out according to the manufacturer's recommendations. The 198 average concentrations of human C5 in the mice were determined as 48.98 gg / mL + 15.1 ug / mL. Prior to antibody dosing, male and female humanized C5 mice were stratified according to human C5 levels that averaged 50 gg / mL. For each anti-C5 mAb, cohorts of five mice received a single subcutaneous (s.c.) injection of 15 mg / hg of H4H12166P, H4H12161P, Comparator 1, or an isotype control. All mice were bled predose, 6 hours, 1, 2, 3, 4, 7, 10, 13, 21, 30, and 45 days postinjection for PK analysis. Furthermore, on day 59 all mice from the poop cohort were sacrificed and terminal hemorrhages were removed for PK and PE analysis). The blood was processed into serum and frozen at -80°C until analyzed. Total antibody concentrations were determined at 12 time points and percent hemolysis activity at 1 time point over a 59-day lifetime. The total serum antibody concentrations for each anti-C5 antibody are summarized in Table 29. The mean profiles of total antibody concentration versus time are shown in Figure 6. The mean PK parameters are described in Table 30. □7 / 1 nn / C7n7 / B / v 199 Table 29: Mean serum total IgG concentrations after a single subcutaneous injection of 15 mg / kg of selected anti-C5 antibodies in humanized C5 mice τ Time Ab serum concentration (ug / mL(. Mean + SD (day) 1141112166P | II4II12161P Comparator 1 ί Control isotype 0 NI) NI) NI) j NI) 0.25 31.21.4.2 ) 43.5116.3 59.2124.1 ! 61.5x29.4 1 149.9116.1 193.81:24.1 179.019.8 i 218.1+17 2 160.8x20 221:26.5 166.6±22.3 i 188.8125.8 3 166.2.112.4 210131.2 15 9.2±33.2 ' 177.9126.2 7 158.6+8.5 162.5x34. 8 136.1 138.1 184.9+33.9 10 123.5128.7 133.2+20.2 107.2145.7 159.5 128.8 13 93.7+23.6 97.2124.6 70.6138 117.2124.1 21 60.41 14.9 42.4x30.3 29.5:120.6 80.0.117.5 30 37.8110.8 15.3+19.7 4.2±3.5 42.1 + 6.7 45 20.715.2 3.515.2 0.410.3 16.5 H 3.9 59 4.111.9 0.6H.0 0.0810.04 4.614.5 Time = Time in hours after injection of a single dose; Day = Study day; SD = standard deviation; SEM = standard error of the mean; ND = Not detected; NS = No sample. Table 30: PK parameters Parameter Units Test antibody (mean + SD) Comparator 1 Isotype Control H4H12166P H4H12161P Cmax pg / mL 178 i 10 225 i 22 183 i 18 221 i 19 AUClast d.pg / mL 3490 a 590 3040 χ 900 2240 t 780 4080 - 480 tl'2 I) 11 + 1 5.8 t 2 4.2 i 1 9.9 t 4 'gonna: Maximum concentration; AUC area under the concentration-time curve; AU C iast AUC calculated from time 200 zero until the time of the last positive concentration; Tb = estimated observed half-life. Mean concentration versus time profiles show that H4H12166P, H4H12161P, Comparator 1, and isotype control reached a maximum serum concentration (Cmax) between days 1 to 3, with Cmas values ​​comparable within 1.3-fold (178, 225, 183 and 221) pg / mL, respectively. H4H12166P and the isotype control had similar clearance profiles, with remaining drug levels of approximately 4 pg / ml at day 59. H4H12161P exhibited more rapid clearance than that of H4H12166P and isotype control, but was eliminated more slowly than the isotype control. Comparator 1. On day 59, H4H12161P had a mean serum drug level of 0.6 pg / mL, while Comparator 1 had a nearly undetectable drug level of 0.08 pg / mL. The isotype control, H4H12166P and H4H12161P exhibited comparable exposure values ​​(AUCiast) within 1.3 times (4080, 3490 and 3040 days- pg / mL, respectively) while Comparator 1 exhibited a 1.6-fold lower exposure (2240 ​​days- pg / mL, respectively). pg / mL) compared to H4H12166P. Example 12: LC-MRM-MS Based Assay to Determine Total Human C5 Concentration In this Example, serum C5 concentrations 07 / I ηη / Ρ7Π7 / Β / ν total human were determined using chromatography 201 liquid coupled to a multiple reaction monitoring mass spectrometry (LC-MRM-MS) method in a pharmacokinetic / pharmacodynamic study of anti-C5 antibody H4H12166P. Serum concentrations of total human C5 were determined by measuring the concentration of a 10 amino acid peptide contained in the C5 sequence LQGTLPVEAR (aa 11291138 of SEQ ID NO: 359) as a proxy for C5. Theoretically, this method could also detect the split product C5, C5b. However, due to the instability of free C5b, C5b concentrations in serum are generally low and the majority of C5b is bound to cell surfaces in the form of MAC complexes (Cooper and Muller-Eberhard 1970, J. Exp. Mcd . 132: 775 -93; Haddcrs ct al 2012, Ccll Rcp. 1: 2007). Therefore, the processed serum samples analyzed here are likely to contain only negligible amounts of C5b product, if any. Methods For the PK / PD study, mice received a single dose of 15 mg / kg of H4H12166P by subcutaneous (s.c.) injection. All mice were bled before injection and one day after injection for PK analysis. Furthermore, at 10, 20, 30, 40, 50, and 60 days after injection, the mice were sacrificed and □7 / 1 nn / C7n7 / B / v 202 terminal hemorrhages were removed for PK and PD analysis. Human C5 was used as a reference standard for calibration; and a human C5 peptide produced with a C-terminal stable isotope-labeled arginine residue was used as an internal standard (LQGTLPVEAR—l3C¿15N4). The reference standard was used at concentrations ranging from 3.9 to 250 pg / mL (1:2 serial dilutions) in serum from home-generated C5 knockout mice, in which the mouse C5 gene was deleted (C5- / -) . Serum from C5 − / − mice was also used as a negative control (blank). Calibration standards, blanks, and study serum samples (10 pL each) were dried and then denatured in 100 pL of 8M urca / 20 mM Tris(2-carboxyctyl)phosphine (TCEP) buffer at 37°C. for 1 hour. Next, 10 pL of 25 nM internal standard was added to all samples. Samples were alkylated with 10 rriM 2-iodoacetamide at room temperature for 30 minutes and were diluted with 50 mM ammonium bicarbonate to a final volume of 500 pL. The samples were then digested with trypsin (1:20 w / w) overnight at 37°C. The C5-derived tryptic peptide LQGTLPVEAR was detected and quantified by LC-MRM-MS using a Waters Xevo TQ-S system with ACQUITY UPLC. Each processed sample (10 pL) was injected into a □7 / 1 nn / C7n7 / B / v column. 203 ACQUITY UPLC BEH C18 pre-balanced. The flow rate was 0.6 mL / min (Mobile phase A: water:formic acid / 100:0.1 [V:V] and Mobile phase B: acetonitrile:formic acid / 100:0.1 [V:V]). Retention time and peak area were determined using Masslynx Analyst Data software (Waters). C5 analyte concentrations were calculated from the calibration curve that was constructed by representing the ratio of the peak area of ​​the C5 reference standard (unlabeled C5 peptide LQGTLPVEARi2C¿i4N4 generated by tryptic digestion of hC5) to the internal standard (labeled C5 peptide with stable isotopes) versus the nominal concentration of the C5 reference standard. Concentrations were calculated by linear regression. The lowest concentration of the C5 reference standard (3.9 gg / mL) was within the dynamic range of the assay and was defined as the LLOQ of the assay. Results Concentrations of human ootal C5 in serum were evaluated for samples collected and by tail bleeding before dosing (pre-dose) and by terminal bleeding on days 10, 30 and 35, of the corresponding animals. Total hC5 concentrations following H4H12166P administration were similar (within ~1 to 0.9-fold) to pre-dose levels at days 10, 07 / I ηη / Ρ7Π7 / Β / ν 204 and 35 after administration. The minor differences observed were not statistically significant as assessed; by the Mann-Whitney test using GraphPad Prism software. Analysis of the C5 / H4H12166P molar ratio demonstrated that H4H12166P remained in molar excess of C5 until day 35 post-dosing (Table 31). Table 31: Summary of H4H12166P DP characteristics Day post dose % CP Hemolysis Mean + SD % Inhibition Pre-dose C5 (pg / mL) Terminal ' H4H12166P Terminal molar ratio C5: H4H12166P Fold change (ugTnL) mean + SD 0 77.2 0 n / a n / a n / a 10 5.2 93 34.2 30.0 1.0 78.8 0.3 30 7.4 90 31.9 28.4 0.9 30.4 0.8 35 6.0 92 36.1 32.7 1.0 29.6 0.9 40 ! 37.1 52 n / a 20.9 n / a 50 i All animals in group excluded due to titers MAHA > 1000 t 60 ί ~ 73.57 5 n / a 5.9 n / a aThe percentage of inhibition of the hemolytic activity of CP was calculated from the mean % of CP hemolysis values ​​on the indicated day post-dose in relation to the mean % value of CP hemolysis on day 0.bChange of fold = terminal (indicated day post-dose) C5: pre-dose C5. SD = standard deviation; MAHA = mouse anti-human antibody; n / d = not determined Animals with data impacted by MAHA were excluded 205 completely from the calculations (2x day 30, 1 x day 35, 2 x day 40 and all 4 mice on day 50). Example 13: Epitope Mapping of H4H12166P Binding to C5 by Hydrogen / Deuterium Exchange H / D exchange epitope mapping with mass spectrometry was carried out to determine the amino acid residues of hC5 [(amino acids MI -CI676 of SEQ ID NO: 359) with which H4H12166P interacts. A general description of the H / D exchange method is set out, for example, in Ehring (1999) Analytical Biochemistry 267 (2): 252-259; and Engen and Smith (2001) Anal. Chem 73:256A-265A. HDX-MS experiments were carried out on a Waters HDX / MS integrated platform, consisting of a Leaptec HDX PAL system for deuterium labeling, a Waters Acquity M-Class (auxiliary solvent manager) for digestion and loading of the sample, a Waters Acquity MClass (pBinary solvent manager) for the analytical column gradient, and the Synapt G2-Si mass spectrometer for peptic peptide mass measurement. The labeling solution was prepared in a 10 mM PBS buffer in DsO at pD 7.0 (equivalent to pH 6.6). For deuterium labeling, 3.8 gL of C5 (6 pmol / pL) or premarketed C5 was incubated with the antibody at a molar ratio of 206 1:1 with 56.2 pL D2O of labeling solution for various time points (e.g., non-cleared control = 0 sec, labeling for 1 min and 20 min). Deuteration was stopped by transferring 50 pL of samples to 50 pL of a pre-chilled quench buffer (0.2 M TCEP, 6M guanidine chloride in 100 mM phosphate buffer, pH 2.5) and the mixed sample was incubated at 1.0°C for two minutes. The quenched sample was then injected into a Waters HDX manager for online pepsin / protease XIII digestion. The digested peptides were trapped on an ACQUITY UPLC BEH C18 1.7- pm, 2.1 x 5mm VanGuard Pre-column at 0°C and eluted on an ACQUITY UPLC BEH C18 1.7- pm, 1.0 x 50 mm analytical column for gradient separation. 9 minutes of 5% - 40% B (mobile phase A: 0.1% formic acid in water, mobile phase B: 0.1% formic acid in acetonitrile). The mass spectrometer was set to a cone voltage of 37 V, scan time of 0.5 s, and mass / charge range of 50–1700 Thomson units (Th). For identification of human C5 peptides, LC-MSE data from the non-deuterated sample were processed and the database including human C5, pepsin and their random sequence were searched through Waters ProteinLynx Global Server (PLGS) software. ). The identified peptides were imported into the □7 / 1 nn / C7n7 / B / v software. 207 DynamX and were filtered by two criteria: (1) minimum products per amino acid = 0.3 and (2) replication file threshold =3. The DynamX software automatically determined the deuterium uptake of each peptide based on retention time and high mass precision (<10ppm¡ at multiple time points with 3 replicates at each time point. Using the pepsin / protease XIII online column coupled with MSE data acquisition, 189 total human C5 peptides were identified in the absence or presence of the antibody, representing 62% sequence coverage. Five peptides had significantly reduced deuteration uptake (centroid delta values ​​> 0.9 daltons with p values ​​< 0.05) when bound to H4H12166P and are illustrated in Table 32. Table 32: Deuteration of human C5 peptides upon binding to H4H12166P Imin Deuteration 20 min Deuteration Residues ρς C51H4H12166P A (15 C5-H4H12166P A Centroid H+ Centroid MH* Centroid MH+ Centroid MH+ 591-599 1015.38+0.09 1014.4410.16 -0.93 1015.64+0.04 101 4.60.· 0.08 -1.04 593-599 769.41+θΊ 1 768.33+0.05 -1.08 769.65+0.01 768.30+0.004 -1.35 775-787 1693.81+0.11 1692.85+0.07 -0.96 1694.06+0.04 1692.96+0.02 -1.10 775- 794 2439.62+0.29 2438.42+0.20 -1.20 2440.16+0.06 2439.17+0.21 -0.99 779-787 1141.14+0.04 1140.21+0.05 -0.93 1141.23+0.03 1140.21 + 0.02 -1.02 The recorded peptide mass corresponds to the average value of the MH+centroid mass from three repetitions. These peptides, corresponding to the 208 amino acids 591-599 and 775-794, had a slower deuteration rate upon binding to H4H12166P. These identified residues also correspond to residues 591-599 and 775-794 of human C5 as defined in Uniprot entry P01031 (C05_HUMAN; SEQ ID NO: 359). Example 14: Effect of anti-C5 antibodies on ocular inflammation in experimental autoimmune uveitis in mice The present study was performed to evaluate the role of C5 in experimental autoimmune uveitis (EAU). Both genetic [C5 knockout (KO), C3 / C5 double KO mice] and pharmacological (anti-C5 antibody) experimental approaches were used. Methods Adult C57BL / 6J (n = 25, Jackson Laboratories), C5 KO (n = 13), and C3 / C5 KO (n = 8) mice (Regeneren Pharmaceuticals Inc.) were used. UAE was induced by subcutaneous injection of human interphotoreceptor retinoid binding protein peptide (IRBP) in complete Freund's adjuvant and intraperitoneal injection of pertussis toxin. The anti-mouse C5 mAb or the isozyme control mAb were administered via subcutaneous poop injections 3 days from day 5 to 28. The anti-mouse C5 antibody used in this study 209 (Μ1Μ17628Ν) comprised an HCVR / 2CVR of SEQ ID NO: 362 / 363. SPECTRALIS® HRA + OCT (Heidelberg Engineering, Inc.) was used to assess inflammation levels on days -1, 7, 14, 21, and 28. All animals were sacrificed on day 28 for blood and eye collection. A hemolysis assay with / without human C3 was performed to validate complement inhibition. The data were analyzed by ANOVA. Results Compared with wild-type mice, the occurrence of inflammation (30-50%) and vitreous cell cluster counts were significantly decreased in 05 KO mice (ρ<0.01). Optical coherence tomography (OCT) scores in C5 KO mice were also significantly reduced by 50% at week 3 (ρ < 0.0001). Interestingly, in C3 / C5 double KO mice, there were significantly more vitreous cell clusters and higher disease scores at day 28 compared to wild-type mice (ρ < 0.05). In animals receiving anti-mC5 Ab (50 mg / kg), the incidence of inflammation and vitreous cell groups were significantly lower compared to the untreated group or the isotype control group on day □ 7 / 1 nn / C7n7 / B / v (p <0.01) . At weeks 3 and 4, OCT scores 210 in the group treated with anti-C5 antibodies were significantly lower compared to no treatment or isotype control (p<0.0001). (Figure 7). Hemolysis assays with / without human C3 confirmed the inhibition effect of anti-C5 antibody at week 4 (Figures 8A8B). Conclusion Ocular inflammation due to UAE was mitigated by inhibiting C5 activity, either by genetic deletion or pharmacological inhibition with a specific anti-C5 antibody. C5 depletion delayed the onset of UAE and reduced the OCT disease score. These results indicate that C5 is a potential therapeutic target for autoimmune uvcytis. Anti-C5 antibody has a protective effect on UAE disease in wild-type mice. Our findings also suggest that C3 might be beneficial for UAE disease in mice. Example 15: Effect of human anti-C5 antibodies in experimental autoimmune uveitis This example describes the effects of anti-C5 antibodies against human C5 in a mouse model of experimental autoimmune uveitis (EAU). The mice used for this study were humanized to express the C5 □7 / 1 nn / C7n7 / B / v protein. 211 human using Velocigene® technology (Valenzuela et al 2003, Nat. Biotechnol. 21: 652-659). Humanized mice were engineered to replace exon 2 through exon 41 of the murine C5 gene with exons 2 through 42 of the human C5 gene (described in United States Patent Application Publication 2015 / 0313194, incorporated herein in its entirety ). Methods Adult male mice were immunized subcutaneously in each thigh with 150 µg of human interphotoreceptor retinoid binding protein (IRBP) peptide 1-20 (GPTHLFQPSLVLDMAIV / LLD) (SEQ ID NO: 364) (Avichezer et al 2000, Invest. Ophthalmol. Vis. Sci. 41: 127-131) in 0.2 ml of CFA emulsion, supplemented with the Mycobactcrium tuberculosis H37RA strain at 2.5 mg / ml. The mice were then inoculated intraperitoneally with 1.0 pg of pertussis toxin (PTX) to facilitate the induction of cell-mediated antiimmunity by promoting a Thl polarization of the immune response (Thurau et al 1997, Clin. Exp. Immunol. 109: 370-376 ; Silver) et al 1999, Invest. Ophthalmol. Vis. Sci. 40: 2898-2905). The body weights of the animals were monitored twice a week. Ophthalmological examinations were carried out on day -1, before UAE induction and on days 7, 14, 21 and 28. Mice were anesthetized with ketamine (120 212 mg / kg, IP) and xylazine (5 mg / kg, IP). Pupils were dilated using 0.5% Tropicamide ophthalmic solution and the fundus was examined with a contact lens with a fundus camera on a retinal angiography (HRA) platform + OCT system Spectralis Heidelberg (Heidelberg Engineering, Carlsbad, CA, USA). A series of 61 lateral optical sections were obtained for each eye using the OCT function on the Spectralis HRA + OCT system (Heidelberg Engineering, Carlsbad, CA, USA). The OCT imaging area was centered on the optic disc, allowing equal images to be obtained above and below the optic nerve head. Retinal thickness was measured as the distance between the bottom of the RPE layer and the inner limiting membrane of the eye. Measurements were taken at 1500 pm from the optic disc, and values ​​from 4 different retinal quadrants (e.g., superior, inferior, temporal, and nasal) were averaged for a mean retinal thickness of the eye. The severity of inflammatory cell infiltration into the vitreous was also graded on OCT images, by assessing the average number of inflammatory cell clusters in the vitreous, across four lateral OCT scans that transected the optic nerve, per eye. □7 / 1 nn / C7n7 / B / v 213 A 4-point scale was developed to assess disease severity on OCT images (OCT scores) (Table 33). Table 33: In vivo UAE score by Optical Coherence Tomograph 5 (OCT) □7 / 1 nn / cznz / b / v Grade Criterion 0 No change 0.5 (Trace) Infiltration of minor inflammatory cells in the vitreous, mainly near the head of the optic nerve (<15 groups) 1 Infiltration of minor inflammatory cells in the vitreous, mainly near the head of the optic nerve ( <25 groups); minor subrelinal focal lesions (gray spots) in the periphery; minor retinal folds in the periphery; retinal vascular dilation; Perivasculitis and vasculitis. Moderate inflammatory cell infiltration in the vitreous more diffuse, but not in the far periphery (<50 groups); disorders of the retinal layer; Small to medium-sized granuloma formations with retinal folds mainly in the periphery; dilation of vessels; minor focal conoid neovascularization; perivasculitis and vasculitis; 214 retinal edema! minor (10 pm) Moderate to severe diffuse inflammatory cell infiltration into the vitreous (<50 clusters); diffuse retinal layer tears and dilated vessels in the inner nuclear layer; Medium to large granuloma formations with retinal folds throughout the retina; severe retinal vascular dilation; perivasculitis and vasculitis; moderate diffuse conoid neovascularization; moderate to severe retinal edema (10-40 pm); minor retinal detachments. 4 Severe diffuse inflammatory infiltration of cells in the vitreous (<7 0 groups); disruptions of the diffuse layer: a and dilated vessels in the inner nuclear layer; Formation of severe diffuse granuloma with retinal folds; severe diffuse choroidal neo-vascularization; perivasculitis and vasculitis; retinal degeneration or severe retinal edema (loss of > 20 pm or gain of > 4 0 pm respectively); Large retinal detachments. 215 Statistic analysis Statistical analyzes for parametric data (body weight, inflammatory cell clusters in the vitreous, and retinal thickness) were performed using one-way ANOVA test and Tukey's multiple comparison test. For non-parametric data (OCT scores and histology scores) analyzes were performed using the Kruskal-Wallis test and Dunn's test with GraphPad Prism software version 5.0d relative to the isotype control or untreated groups. . Data show mean values ​​1 SEM. A ρ value less than 0.05 was considered statistically significant. Results In a first study (Study A), mice were treated subcutaneously every 3 days starting on day 5 with an isotype control antibody (50 mg / kg), or 10 mg / kg or 50 mg / kg. <g de h4h12170p. el tratamiento con 10 mg kg h4h12170p produjo una reducción la inflamación y el daño retiniano (figura 9) . los ratones tratados también mostraron estadísticamente significativa en las puntuaciones oct día 21 28 10).In a second study (study B), mice were treated subcutaneously every 3 days starting on day 6 □7 / 1 nn / C7n7 / B / v 216 with an isotype control - (10 mg / kg), 3 mg / kg or 10 mg / kg H4H12166P, or with Comparator 2 (see Example 2 in this document; Control constructs used in the following Examples). Treatment with H4H12166P at 3 mg / kg or 10 mg / kg produced a dose-related reduction in OCT scores that was statistically significant on days 14 to 28 (Figure 11). Treatment with 10 mg / kg H4H12166P in humanized C5 mice starting 6 days after UAE induction produced a dose-related reduction in retinal inflammation and damage, as determined by OCT obtained on days 14 to 28 (Figure 12). In both studies, non-invasive assessment in life by OCT showed progressive development of inflammation, increased retinal thickness and morphological abnormalities in control animals after immunization with IRBP. Conclusion These experiments provide additional pharmacological evidence that C5 plays a role in the pathogenesis of autoimmune uveitis. Pharmacological depletion of human C5 by fully human anti-human C5 antibodies postponed the incidence of UAE and reduced disease severity, establishing the efficacy of these antibodies in 07 / I ηη / Ρ7Π7 / Β / ν 217 autoimmune uveitis. Example 16: Effect of anti-C5 antibodies on renal ischemia-reperfusion injury The present study was carried out to evaluate the role of C5 in renal ischemia-reperfusion injury. Both genetic (using C3 knockout and C5 knockout mice) and pharmacological (using anti-C5 antibodies) approaches were used. The ischemia-reperfusion model was induced by bilateral renal pedicle clamping for 4 5 minutes, followed by 4 8 h of reperfusion. Sham laparotomy served as a control. Anti-C5 antibody was administered at 50 mg / kg intravenously as a single dose immediately after ischemia (curative); or subcutaneously as two doses, day -1 and surgery day 1 (preventive). The anti-C5 antibody used for this study was M1M17628N comprising HCVR / LCVR of SEQ ID NO: 362 / 363. Blood urea nitrogen (BUN) and serum creatinine markers were used to assess disease and protection levels in the mice. Table 34: Percent change in blood urea nitrogen levels in mice treated with anti-C5 antibody (M1M17628N) in preventive and therapeutic modes 218 BUN, % Chango Vs. RIRI t Veh RIRI i Iso. CU Day 2 Day 2 RIRI -M1M17628N (Prcv) -37.19 -34.68 RIRI + M1M17628N (Cur) - 53.70 -51.85 Table 35: Percent change in serum creatinine levels in mice treated with anti-C5 antibody (M1M17628N) in preventive and therapeutic modes SCr, % Chango Vs. RIRI + Vch RIRI + Iso. CU Day 2 Day 2 RIRI + M1M17628N (Prcv) -53.09 -49.34 RIRI + M1M17628N (Cur) -59.40 -56.16 Compared with wild-type mice, C3 and C5 knockout mice showed significant functional protection in the RIRI model of acute kidney injury, as evidenced by reductions in blood urea nitrogen 10 and serum creatinine levels. The anti-C5 antibody showed functional protection in the RIRI model in both preventive and therapeutic modes (Tables 34-35). Example 17: Effect of anti-C5 antibodies in lupus nephritis This example describes the efficacy of anti-C5 antibodies in the treatment of lupus nephritis in a mouse model. 219 Systemic lupus erythematosus (SLE) is an autoimmune disorder caused by loss of tolerance to autoantigens, production of autoantibodies, and deposition of complement-fixing immune complexes (IC) in injured tissues. SLE is characterized by a wide range of clinical manifestations and specific organs, with lupus nephritis being one of the most serious complications. Complement activation in the kidneys of patients with lupus nephritis contributes to inflammation and tissue damage. The efficacy of anti-C5 antibodies in the treatment of lupus nephritis was studied in NZBWF1 mice, a spontaneous mouse model of lupus nephritis (Yang et al., 1996, PNAS). Mice develop an autoimmune disease resembling human SLE, autoantibodies against nuclear autogens and cell membrane proteins, hypergammaglobulinemia, albuminuria, proteinuria, initiate immune complex glomerulonephritis, and die of renal failure and end-stage renal disease at 35 to 50 weeks of age. . For this study, 25-week-old NZBWF1 mice were treated subcutaneously with 30 mg / kg isotype control, or anti-C5 antibodies twice a week for 8 weeks, followed by three times a week for 10 weeks. Anti-mouse C5 antibodies used for this □7 / 1 nn / C7n7 / B / v 220 study were M1M17628N and M1M17627N, comprising HCVR / LCVR of SEQ ID NO: 362 / 363 and 365 / 366, respectively. Treatment with anti-C5 antibodies significantly improved the survival rate in mice (Figure 13). Both antibodies improved albuminuria at 8-14 weeks of treatment (Figures 14A-14B) and blood urea nitrogen levels at 12-16 weeks of treatment (Figure 15). Example 18: Effect of anti-C5 antibodies against astrocyte cell death Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system (CNS) that primarily affects the optic nerve and spinal cord. In NMO, anti-aquaporin-4 autoantibodies (AQP4-Ab) cause damage to astrocytes by activating complement-dependent cytotoxicity (CDC). The objectives of this study were to evaluate the role of the complement system in the progression of NMO and the use of an antibody against a complement protein as a possible therapeutic treatment for NMO. Primary rat cortical astrocytes were obtained from the cerebral cortex of postnatal rat pups and cultured with AQP4-Ab (rAb-53 antibody from Patent Application Publication NS 2014 / 0170140; Bennett □7 / 1 nn / C7n7 / b / v 221 et al 2009, Ann. Neurol 66: 617-629) and complement proteins to demonstrate cell-mediated cltotoxicity. The experiments were then repeated with the addition of an anti-C5 antibody to demonstrate blocking of astrocyte cell destruction. To quantify cell death, a CytoTox-Glo™ luminescence cytotoxicity assay was performed. The assay used various concentrations of anti-C5 antibody (0.001 pg / ml, 0.01 pg / ml, 0.1 pg / ml, 1 pg / ml, 10 pg / ml, 100 pg / ml, or 1000 pg / ml) or a isotype control. To determine whether anti-C5 antibody could block AQP4-Ab-induced CDC, astrocytes were plated and the CytoToxGlo™ cytotoxicity assay was repeated to find an optimal dose of AQP4-7\b for that plate. The optimal concentration of AQP4-Ab found was 50 pg / ml, and in a subsequent experiment a constant dose of AQP4-Ab (50 pg / ml) was used, while the dose of anti-C5 antibody was varied. As shown in Figure 16, a decrease in RLU (by an average of 300k to an average of 100k) was observed with increasing amounts of anti-C5 antibody, demonstrating that anti-C5 antibody blocks astrocyte cell death. . For both experiments, RLU did not vary with the isotype control antibody. As shown in Figure 16, the □7 / 1 nn / C7n7 / B / v antibodies 222 anti-C5 inhibited Ab-induced cytotoxicity of AQP4 in primary cortical astrocytes with IC50 of 15-17 nM. In a subsequent study, anti-AQP4 antibody and anti-C5 antibody will be injected into the brain of rats to evaluate the therapeutic efficacy against complement-mediated cytotoxicity of astrocytes in the CNS. Example 19: Endothelial assay This example describes an in vitro glomerular endothelial assay to examine whether anti-C5 antibodies block the deposition of C5b-9 and C3. Reproducible methods to evaluate the inhibitory effects of candidate drugs on complement activation are essential for clinical development. Due to the complexity of complement activation pathways, an assay must use relevant cells and endpoints for the given therapeutic indication. Here, using an immortalized human glomerular endothelial cell line (HGEC), a C3 and 05 complement deposition model was validated to evaluate the blocking activity of anti-C3 or C5 nAbs. Methods Primary human kidney glomerular endothelial cells (HGEC; Cell Biologies) were plated overnight in complete media in 96 □7 / 1 nn / C7n7 / B / v plates. 223 wells with transparent black bottom coated with collagen I. Cells were treated with PBS (control) or activated for 10 minutes with 10 μΜ ADP. After washing with PBS, 50% human serum (complement-preserved, C3-depleted, or C5-depleted) was added for 4 hours. Anti-C5 antibodies were added at 1 mg / ml to the serum before treatment. Cells were washed and fixed and probed with anti-C3b antibodies (Thermofisher) and / or anti-C5b-9 antibodies (Abcam), secondary antibodies and counterstained with DAPI. Images were captured in ImagExpress and high-content image analysis was used to quantify fluorescent staining for each image and averaged per condition. Results Deposition of C3 and C5b-9 was observed in ADP-activated HGEC exposed to normal human serum, but not in non-activated HGEC (C3: 1.5 χ 107± 1.0 χ 107; C5: 7.9 χ 106+ 6.6 x 10% P< 0.05 vs HGEC not activated by ADP). The deposition of C3 and C5b-9 was significantly reduced in ADP-activated HGEC exposed to serum depleted at C3 or C5 (C3: 3.3 χ 105± 4.8 χ 104; C5: 1.5 × 10e± 6.0 χ 105, PC0.05). The addition of a blocking anti-C5 mAb significantly reduced the deposition of C5b-9 derived from normal human serum on ADP-activated HGEC, the deposition was comparable to those 224 sera depleted in C5 (mAb C5: 1.02 x 10€+ 6.0 χ 105, Control mAb 3.7 x 10c1 1.6 x 10c, P < 0.05 vs. control mAb). Conclusion These data demonstrate the utility of an in vitro human glomerular endothelial assay for modeling complement C3 and C5 deposition. In addition to in vitro screening, this assay offers potential as a translational model to evaluate anticomplement strategies in kidney disease using patient-derived serum samples. The present invention should not be limited in its scope by the specific embodiments described herein. In fact, various modifications of the invention, in addition to those described herein, will be apparent to those skilled in the art from the foregoing description and the accompanying figures. Such modifications are intended to fall within the scope of the claims< / g>

Claims

1. A method of a human CLAIMS improving at least one disease disorder in which the method comprises a vehicle and component administering a therapeutically effective quantity of an antibody specifically binding to an HCDR1, an HCDR2, an HCDR3, and an LCDR1, LCDR2, and LCDR3. The method comprises a human variable of amino acids comprising ...

2. The method according to claim 1, characterized in that the disease or disorder is selected from the group consisting of atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria, age-related macular degeneration, geographic atrophy, uveitis, neuromyelitis optica, multiple sclerosis, stroke, Guillain-Barré syndrome, traumatic brain injury, Parkinson's disease, a disorder of inappropriate or unwanted complement activation, a complication of nemodialysis, hyperacute allograft rejection, xenograft rejection, interleukin-2-induced toxicity during IL-2 therapy, an inflammatory disorder, inflammation of an autoimmune disease, Crohn's disease, adult respiratory distress syndrome, thermal injuries, burns, frostbite, post-ischemic reperfusion disorder, myocardial infarction, capillary leak syndrome, obesity, diabetes, Alzheimer's disease, schizophrenia,stroke, epilepsy, atherosclerosis, vasculitis, bullous pemphigoid, C3 glomerulopathy, membranoproliferative glomerulonephritis, diabetic nephropathy, Alport syndrome, progressive renal failure, proteinuric kidney disease, renal ischemia-reperfusion injury, lupus nephritis, post-pump syndrome in cardiopulmonary bypass or renal bypass, hemodialysis, renal ischemia, mesenteric artery reperfusion after aortic reconstruction, infectious disease, sepsis, an immune complex disorder, an autoimmune disease, a kidney disorder, rheumatoid arthritis, systemic lupus erythematosus, systemic lupus erythematosus nephritis, proliferative nephritis, hemolytic anemia, asthma, chronic obstructive pulmonary disease, emphysema, pulmonary embolism and infarction, pneumonia and myasthenia gravis.

3. The method according to claim 1, characterized in that the disease or disorder is atypical hemolytic uremic syndrome.

4. The method according to claim 1, characterized in that the disease or disorder is paroxysmal nocturnal hemoglobinuria.

5. The method according to claim 1, characterized in that the pharmaceutical composition is administered in combination with a second therapeutic agent.

6. The method according to claim 5, characterized in that the second therapeutic agent is selected from the group consisting of an anticoagulant, an anti-inflammatory drug, an antihypertensive, an immunosuppressant, a hypolipidemic agent, an anti-CD20 agent, rituximab, an anti-TNF agent, intliximab, an anticonvulsant, a C3 inhibitor, a second anti-C5 antibody, and an antithrombotic agent.

7. The method according to claim 1, characterized in that the pharmaceutical composition is administered subcutaneously, intravenously, intradermally, intraperitoneally, orally, intramuscularly or intracranially.

8. The method according to claim 1, characterized in that the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence set out in SEQ ID No.:

98.

9. The method according to claim 1, characterized in that the antibody or antigen-binding fragment thereof comprises a light chain variable region comprising the amino acid sequence set out in SEQ ID No.

106.

10. The method according to claim 1, characterized in that the antibody or antigen-binding fragment thereof comprises a heavy-chain variable region comprising the amino acid sequence set forth in SEQ ID No. 98 and a light-chain variable region comprising the amino acid sequence set forth in SEQ ID No.

106. □7 / 1 nn / C7n7 / B / v 229 11. The method according to claim 1, characterized in that the antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence of SEQ ID No:

353.

12. The method according to claim 1, characterized in that the antibody or antigen-binding fragment thereof comprises a light chain comprising an amino acid sequence of SEQ ID No:

354.

13. The method according to claim 1, characterized in that the antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence SEQ ID No.: 353; and a light chain comprising an amino acid sequence SEQ ID No.:

354.

14. The method according to claim 13, characterized in that the antibody or antigen-binding fragment thereof is an antibody.

15. The method according to claim 14, characterized in that the disease or disorder is paroxysmal nocturnal hemoglobinuria (PNH).

16. The method according to claim 14, characterized in that the disease or disorder is myasthenia gravis. □7 / 1 nn / C7n7 / B / v 230 17. The method according to claim 14, characterized in that the disease or disorder is neuromyelitis optica.

18. The method according to claim 15, characterized in that the antibody is administered to the subject intravenously and subcutaneously.

19. The method according to claim 16, characterized in that the antibody is administered to the subject intravenously and subcutaneously.

20. The method according to claim 17, characterized in that the antibody is administered to the subject intravenously and subcutaneously.

21. The method according to claim 18, characterized in that the antibody is administered in combination with a second therapeutic agent.

22. The method according to claim 19, characterized in that the antibody is administered in combination with a second therapeutic agent.

23. The method according to claim 20, characterized in that the antibody is administered in combination with a second therapeutic agent.