HUMANIZED ANTI-C1S ANTIBODIES AND METHODS FOR USING THEM

Abstract

This description provides humanized anti-C1s antibodies. This description provides nucleic acids comprising nucleotide sequences encoding the humanized anti-C1s antibodies; and the host cells comprising the nucleic acids. This description provides compositions comprising the humanized anti-C1s antibodies. This description provides methods of use of the humanized anti-C1s antibodies.

Description

HUMANIZED ANTI-C1S ANTIBODIES AND METHODS FOR USING THEM BACKGROUND OF THE INVENTION The complement system is a well-known effector mechanism of the immune response, providing not only protection against pathogens and other harmful agents but also recovery from injury. The complement pathway comprises a number of proteins that typically exist in the body in an inactive form. The classical complement pathway is triggered by activation of the first complement component, referred to as the Cl complex, which consists of the proteins Clq, Clr, and Cls. Upon binding Cl to an immune complex or other activator, the Cls component, a diisopropyl fluorophosphate (DFP)-sensitive serine protease, cleaves the C4 and C2 complement components to initiate activation of the classical complement pathway. The classical complement pathway appears to play a role in many diseases and disorders. BRIEF DESCRIPTION OF THE INVENTION This description provides humanized anti-Cls antibodies. This description provides nucleic acids comprising nucleotide sequences encoding the humanized anti-Cls antibodies; and the host cells comprising the nucleic acids. This description provides compositions comprising the UO3 Ref. 331C81 Humanized anti-Cls antibodies. This description provides methods of use for humanized anti-Cls antibodies. The present description provides a humanized antibody that binds specifically to the Cls component of complement, wherein the antibody comprises: a) a VH region comprising the amino acid sequence: (Q / E)VQL(V / Q)QSGAE(V / L)KKPGASVK(L / V)SC(T / A)ASGFNIKDDYIHWV(K / R)QAPGQGLEWIGRIDPADGHTKYAPKFQVK(V / A)TITADTST(S / N)TAY(L / M)(E / Q) LSSL(R / T)SEDTAVYYCARYGYGREVFDYWGQGTTVTVSS (SEQ ID NO:26); and b) a VL region comprising the amino acid sequence: DIVLTQSPDSLAVSLGERATISCKASQSVDYDGDSYMNWYQQK(T / P)GQPPK(I / L)LIY DASNLESGIPARFSGSGSGTDFTLTISSLE(E / P)EDFA(I / V)YYCQQSNEDPWTFGGGT KVEIK (SEQ ID NO:27). In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO: 10 and b) a VL region comprising SEQ ID NO: 20. In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO: 10 and b) a VL region comprising SEQ ID NO:22.In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO:10 and b) a VL region comprising SEQ ID NO:24. In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO:12 and b) a VL region comprising SEQ ID NO:20. In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO:12 and b) a VL region comprising SEQ ID NO:22. In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO:12 and b) a VL region comprising SEQ ID NO:24. In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO:14 and b) a VL region comprising SEQ ID NO:20. In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO:14 and b) a VL region comprising SEQ ID NO:22.In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO:14 and b) a VL region comprising SEQ ID NO:24. In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO:16 and b) a VL region comprising SEQ ID NO:20. In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO:16 and b) a VL region comprising SEQ ID NO:22. In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO:16 and b) a VL region comprising SEQ ID NO:24. In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO:18 and b) a VL region comprising SEQ ID NO:20. In some cases, the antibody comprises: a) a VH region comprising SEQ ID NO:18 and b) a VL region comprising SEQ ID NO:22. In some cases, the antibody. ML / a / ZUZZ / UU I UO3 comprises: a) a VH region comprising SEQ ID NO:18 and b) a VL region comprising SEQ ID NO: 24. In some cases, the humanized antibody is selected from the group consisting of a Fab fragment, an F(ab')2 fragment, an scFv, an Fv. In some cases, the humanized antibody comprises a heavy chain constant region of the IgG1, IgG2, IgG3 or IgG4 isotypes. This description provides a composition comprising: a) a humanized antibody as described above and below; and b) a pharmaceutically acceptable excipient. In some cases, the composition comprises one or more of a tonicity agent, a suspending agent, an emulsifying agent, a stabilizer, a preservative, a lyoprotectant, a surfactant, and a sugar. This description also provides a container comprising the composition described herein. In some cases, the container is sterile. In some cases, the container is a vial, a bottle, or a syringe. This description provides a method for reducing the level of a complement component cleavage product in an individual (e.g., in a fluid, tissue, or organ of the individual). The method comprises administering to the individual a humanized antibody of this description as described above or below, or a composition of this description as described above or below, in an amount effective to inhibit complement components and reduce the level of the cleavage product. In some cases, the complement component cleavage product is a C4 cleavage product (e.g., C4b). In some cases, the complement component cleavage product is a C2 cleavage product (e.g., C2a). In some cases, the complement component cleavage product is a C3 cleavage product. In some cases, the individual is a human. In some cases, administration is intravenous.In some cases, administration is intramuscular. In some cases, administration is intrathecal. In some cases, administration is subcutaneous. In some cases, reducing the level of a complement component cleavage product is effective in treating a complement-mediated disorder. In some cases, the complement-mediated disorder is an alloimmune disorder. In some cases, the complement-mediated disorder is an autoimmune disorder. This description provides a method for inhibiting C1-mediated cleavage of a complement component in an individual, wherein the method comprises administering to the individual a humanized antibody of this description as described above or below, or a composition of this description as described above or below, in an amount effective to inhibit C1-mediated cleavage of a complement component. In some cases, the individual is a human. In some cases, the administration is intravenous. In some cases, the administration is intramuscular. In some cases, the administration is intrathecal. In some cases, the administration is subcutaneous. In some cases, inhibition of C1-mediated cleavage of a complement component is effective for treating a complement-mediated disorder. In some cases, the complement-mediated disorder is an alloimmune disorder.In some cases, complement-mediated disorder is an autoimmune disorder. This description provides a method for treating a complement-mediated disorder or disease in an individual, wherein the method comprises administering to the individual a humanized antibody of this description as described above or below, or a composition of this description as described above or below, in an amount effective to treat the complement-mediated disorder or disease. In some cases, the complement component cleavage product is a C3 cleavage product. In some cases, the individual is a human. In some cases, administration is intravenous. In some cases, administration is intramuscular. In some cases, administration is intrathecal. In some cases, administration is subcutaneous. In some cases, reducing the level of a complement component cleavage product is effective in treating a complement-mediated disorder.In some cases, complement-mediated disorders are alloimmune disorders. In some cases, complement-mediated disorders are autoimmune disorders. BRIEF DESCRIPTION OF THE FIGURES FIGURE 1 describes an amino acid sequence of the humanized VH variant 1 (SEQ ID NO:10) and a nucleotide sequence (SEQ ID NO:11) that encodes it. FIGURE 2 describes an amino acid sequence of the humanized VH variant 2 (SEQ ID NO:12) and a nucleotide sequence (SEQ ID NO:13) that encodes it. FIGURE 3 describes an amino acid sequence of the humanized VH variant 3 (SEQ ID NO:14) and a nucleotide sequence (SEQ ID NO:15) that encodes it. FIGURE 4 describes an amino acid sequence of the humanized VH variant 4 (SEQ ID NO:16) and a nucleotide sequence (SEQ ID NO:17) that encodes it. FIGURE 5 describes an amino acid sequence of the humanized VH variant 5 (SEQ ID NO:18) and a nucleotide sequence (SEQ ID NO:19) that encodes it. FIGURE 6 describes an amino acid sequence of the humanized Vk variant 1 (SEQ ID NO:20) and a sequence of UO3 nucleotides (SEQ ID NO:21) that encode it. FIGURE 7 describes an amino acid sequence of the humanized Vk variant 2 (SEQ ID NO:22) and a nucleotide sequence (SEQ ID NO:23) that encodes it. FIGURE 8 describes an amino acid sequence of the humanized Vk variant 5 (SEQ ID NO:24) and a nucleotide sequence (SEQ ID NO:25) that encodes it. FIGURE 9 provides Table 2, which shows the amino acid differences between VH variants of parental TNT005 and example humanized VH. FIGURE 10 provides Table 3, which shows the amino acid differences between VL variants of parental TNT005 and example humanized VL. Figure 11 provides Table 4, which shows the binding properties of humanized variants of TNT005. Data for direct binding to activated Gis (aCls), competitive binding with biotinylated TNT005 50 pM (Biot-005), and inhibition of the classical complement pathway are shown. Figure 12 provides Table 5, which shows the binding properties of humanized variants of TNT005. Affinity data are provided for the binding of humanized variants of TNT005 to active human Gis. FIGURE 13 provides an amino acid sequence UO3 of human Gis. FIGURE 14 describes a pharmacokinetic (PK) profile of a humanized TNT005 variant in cynomolgus monkeys dosed in Phase 1 (Day 1 - Day 43). FIGURE 15 describes a pharmacokinetic profile of a humanized TNT005 variant in cynomolgus monkeys dosed in Phase 1 (Day 32-Day 43). FIGURE 16 describes classical pathway activity of serum from cynomolgus monkeys dosed in Phase 1 (Day 1 - Day 43). FIGURE 17 describes a PK and pharmacodynamic (PD) profile of a humanized TNT005 variant in Phase 2 dosed cynomolgus monkeys (subcutaneous administration of 4 mg / kg daily for 7 days). DETAILED DESCRIPTION OF THE INVENTION Definitions The terms antibodies and immunoglobulin include antibodies or immunoglobulins of any isotype, antibody fragments that retain specific antigen binding, including, but not limited to, Fab, Fv, scFv, and Fd fragments, chimeric antibodies, humanized antibodies, single-chain antibodies (scAb), single-domain antibodies (dAb), single-domain heavy-chain antibodies, a single-domain light-chain antibody, bispecific antibodies, multispecific antibodies, and fusion proteins comprising an antigen-binding portion (also referred to herein as the antigen-binding portion) of an antibody and a non-antibody protein. Antibodies may be detectably labeled, for example, with a radioisotope, an enzyme that generates a detectable product, a fluorescent protein, and the like.Antibodies may be further conjugated with other fragments, such as members of specific binding pairs, for example, biotin (member of the biotin-avidin specific binding pair), and the like. Antibodies may also be bound to a solid support, including, but not limited to, polystyrene plates or beads and the like. The term also encompasses Fab', Fv, F(ab')2, and / or other antibody fragments that retain specific antigen binding, and monoclonal antibodies. As used herein, a monoclonal antibody is an antibody produced by a group of identical cells, all of which were produced from a single cell by repeated cell replication. That is, the cell clone produces only one type of antibody.While a monoclonal antibody can be produced using hybridoma production technology, other production methods known to those skilled in the art can also be used (e.g., antibodies derived from antibody phage expression libraries). An antibody can be monovalent or bivalent. An antibody can be a monomer. Ig, which is a Y-shaped molecule consisting of four polypeptide chains: two heavy chains and two light chains connected by disulfide bonds. The term humanized immunoglobulin or humanized antibody, as used herein, refers to an immunoglobulin comprising parts of immunoglobulins from different sources, where at least one part comprises amino acid sequences of human origin. For example, the humanized antibody may comprise parts derived from a non-human immunoglobulin with the required specificity, such as from a mouse, and from immunoglobulin sequences of human origin (e.g., chimeric immunoglobulin), chemically linked by conventional techniques (e.g., synthetic) or prepared as a contiguous polypeptide using genetic engineering techniques (e.g., the DNA encoding the protein parts of the chimeric antibody may be expressed to produce a contiguous polypeptide chain).Another example of a humanized immunoglobulin is an immunoglobulin containing one or more immunoglobulin chains comprising a CDR derived from a non-human antibody and a frame region derived from a human light and / or heavy chain (e.g., CDR-grafted antibodies with or without frameshifting). These are CDR-grafted or chimeric single-chain antibodies. ML / a / ZUZZ / UU I UO3 are also encompassed by the term humanized immunoglobulin. See, for example, Cabilly et al., U.S. Patent No. 4,816,567; Cabilly et al., European Patent No. 0,125,023 Bl; Boss et al., U.S. Patent No. 4,816,397; Boss et al., European Patent No. 0,120,694 Bl; Neuberger, MS et al., WO 86 / 01533; Neuberger, MS et al., European Patent No. 0,194,276 Bl; Winter, U.S. Patent No. 5,225,539; Winter, European Patent No. 0,239,400 Bl; Padlan, EA et al., European patent application no. 0,519,596 Al. See also, Ladner et al., US patent no. 4,946,778; Huston, US patent no. 5,476,786; and Bird, RE et al., Science, 242: 423-426 (1988)), regarding single-chain antibodies. For example, humanized immunoglobulins can be produced using recombinant and / or synthetic nucleic acids to prepare genes (e.g., cDNA) encoding the desired humanized strand. For example, nucleic acid sequences (e.g., DNA) encoding humanized variable regions can be constructed using PCR mutagenesis methods to alter DNA sequences encoding a humanized or human strand, such as a DNA model of a previously humanized variable region (see, for example, Kamman, M., et al., Nuci. Acids Res., 17: 5404 (1989)); Sato, K., et al., Cancer Research, 53: 851-856 (1993); Daugherty, BL et al., Nucleic Acids Res., 19(9): 2471-2476 (1991); and Lewis, AP and JS Crowe, Gene, 101: 297-302 (1991)). Using these or other suitable methods, variants can also be easily produced. For example, cloned variable regions can be mutagenized, and variants encoding sequences with the desired specificity can be selected (e.g., from a phage library; see, for example, Krebber et al., U.S. Patent No. 5,514,548; Hoogenboom et al., WO 93 / 06213, published April 1, 1993). Antibody fragments comprise a portion of an intact antibody, for example, the variable or antigen-binding region of the intact antibody. Examples of antibody fragments include Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies (Zapata et al., Protein Eng. 8(10): 1057-1062 (1995)); domain antibodies (dAb; Holt et al. (2003) Trends Biotechnol. 21:484); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments. Papain digestion of antibodies yields two identical antigen-binding fragments, called Fab fragments, each with a single antigen-binding site, and a residual Fe fragment, a designation that reflects its ability to crystallize rapidly. Treatment with pepsin provides an F(ab')2 fragment that has two antigen-binding sites and is still capable of cross-linking the antigen. Fv is the minimal antibody fragment that contains a complete antigen recognition and binding site. This region consists of a dimer of a heavy-chain variable domain and a light-chain variable domain in close, non-covalent association. It is in this configuration that the three CDRs of each variable domain interact to define an antigen-binding site on the surface of the Vr-Vl dimer. Together, the six CDRs confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of Fv, comprising only three antigen-specific CDRs) has the ability to recognize and bind the antigen, albeit at a lower affinity than the entire binding site. The Fab fragment also contains the light chain constant domain and the first heavy chain constant domain (CHi). Fab fragments differ from Fab' fragments by the addition of a few residues at the carboxyl terminus of the heavy chain CHi domain, which includes one or more cysteines from the antibody hinge region. Fab'-SH is the designation used herein for Fab' fragments in which the cysteine ​​residues of the constant domains bear at least one free thiol group. F(ab')2 antibody fragments were originally produced as pairs of Fab' fragments with hinge cisternae between them. Other chemical couplings of antibody fragments are also known. The light chains of antibodies (immunoglobulins) from any vertebrate species can be assigned to one of two distinct types, called kappa and lambda, based on the amino acid sequences of their constant domains. Based on the amino acid sequence of the constant domain of their heavy chains, immunoglobulins can be assigned to different classes. There are five main classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these classes can be further divided into subclasses (isotypes), for example, IgG1, IgG2, IgG3, IgG4, IgA, and IgA2. Subclasses can be further divided into types, for example, IgG2a and IgG2b. Single-chain Fv antibody fragments, or scFv, comprise the Vh and Vl domains of the antibody, where these domains are present in a single polypeptide chain. In some embodiments, the Fv polypeptide further comprises a polypeptide linkage between the Vh and Vl domains, which allows the sFv to form the desired structure for antigen binding. For a summary of sFv, see Plückthun in *The Pharmacology of Monoclonal Antibodies*, vol. 113, Rosenburg and Moore, eds. ML / a / ZUZZ / UU I UO3 Springer-Verlag, New York, pp. 269-315 (1994). The term diabodies refers to small antibody fragments with two antigen-binding sites, where the fragments comprise a heavy-chain variable domain (Vh) linked to a light-chain variable domain (Vl) on the same polypeptide chain (Vh-Vl). By using a linker that is too short to allow pairing between two domains on the same chain, the domains are forced to pair with complementary domains on another chain, thus creating two antigen-binding sites. Diabodies are described in more detail in, for example, EP 404,097; WO 93 / 11161; and Hollinger et al. (1993) Proc. Nati. Acad. Sel. USA 90:6444-6448. As used herein, the term affinity refers to the equilibrium constant for the reversible binding of two agents (e.g., an antibody and an antigen) and is expressed as a dissociation constant (Kd). Affinity may be at least 1 times greater, at least 2 times greater, at least 3 times greater, at least 4 times greater, at least 5 times greater, at least 6 times greater, at least 7 times greater, at least 8 times greater, at least 9 times greater, at least 10 times greater, at least 20 times greater, at least 30 times greater, at least 40 times greater, at least 50 times greater, at least 60 times greater, at least 70 times greater, at least 80 times greater, at least 90 times greater, at least 100 times greater, or at least 1000 times greater, or more, than the affinity of an antibody for unrelated amino acid sequences. The affinity of an antibody with respect to a target protein can be, for example, from around 100 nanomolar (nM) to around 0.1 nM, from about 100 nM to about 1 picomolar (pM), or from about 100 nM to about 1 femtomolar (fM) or more. As used herein, the term avidity refers to the resistance of a complex of two or more agents to dissociation after dilution. The terms immunoreactive and preferentially binds are used interchangeably with respect to antibodies and / or antigen-binding fragments. The term binding refers to a direct association between molecules due to, for example, covalent, electrostatic, hydrophobic, and ionic interactions and / or hydrogen bonding, including interactions such as salt bridges and water bridges. A humanized anti-Cls antibody of the present description binds specifically to an epitope within a Cls complement protein. Specific binding refers to binding with an affinity of at least approximately 10⁻⁷ M or greater, for example, 5 x 10⁻⁷ M, 10⁻³ M, 5 x 10⁻⁸ M, and greater. Nonspecific binding refers to binding with an affinity less than approximately 10⁻⁷ M, for example, binding with an affinity of 10⁻⁶ M, 10⁻⁵ M, and greater. IO-4M, etc. As used herein, the term CDR or complementarity-determining region is intended to mean the non-contiguous antigen that combines sites found within the variable region of both heavy-chain and light-chain polypeptides. CDRs have been described by Kabat et al., J. Biol. Chem. 252:6609-6616 (1977); Kabat et al., U.S. Department of Health and Human Services, Sequences of proteins of immunological interest (1991) (also referred to herein as Kabat 1991); by Chothia et al., J. Mol. Biol. 196:901-917 (1987) (also referred to herein as Chothia 1987); and MacCallum et al., J. Mol. Biol. 262:732-745 (1996), where the definitions include overlap or subsets of amino acid residues when compared to each other.However, the application of any definition to refer to a CDR of an antibody or grafted antibodies or variants thereof is included within the scope of the expression as defined and used herein. The amino acid residues, encompassing the CDRs, as defined by each of the references cited above are set out for comparison in Table 1 below. The CDRs described in Figures 1-8 were. UO3 defined according to Kabat 1991. ινΐΛ / a / zuzz / uu i uoo Table 1: CDR Definitions Kabat1 Chothia2 MacCallum3 Vh CDR-1 31-35 26-32 30-35 Vh CDR-2 50-65 53-55 47-58 Vh CDR-3 95-102 96-101 93-101 Vl CDR-1 24-34 26-32 30-36 VL CDR-2 50-56 50-52 46-55 VL CDR-3 89-97 91-96 89-96 The numbering of waste follows the nomenclature of Kabat et al., supra The numbering of residues follows the nomenclature of Chothia et al., supra The numbering of waste follows the nomenclature of MacCallum et al., supra As used herein, the terms CDR-L1, CDR-L2, and CDR-L3 refer, respectively, to the first, second, and third CDRs in a light-chain variable region. As used herein, the terms CDR-H1, CDR-H2, and CDR-H3 refer, respectively, to the first, second, and third CDRs in a heavy-chain variable region. As used herein, the terms CDR-1, CDR-2, and CDR-3 refer, respectively, to the first, second, and third CDRs of the variable region of either chain. As used herein, the term frame (FR) when used in reference to an antibody variable region is intended to mean all amino acid residues outside the CDR regions within the variable region of an antibody. A variable region frame is generally a discontinuous amino acid sequence of approximately 100–120 amino acids in length, but the term FR is intended to refer only to those amino acids outside the CDRs. As used herein, the term frame region is intended to mean each domain of the frame that is separated by the CDRs. A light-chain variable region (VL region) may have four frame regions: FR1, FR2, FR3, and FR4. Similarly, a heavy-chain variable region (VH region) may have four frame regions: FR1, FR2, FR3, and FR4. An isolated antibody is one that has been identified and separated and / or recovered from a compound in its natural environment. Contaminating components in its natural environment are materials that would interfere with the antibody's diagnostic or therapeutic uses and may include enzymes, hormones, and other protein or non-protein solutes. In some modalities, the antibody will be purified (1) to greater than 90%, greater than 95%, or greater than 98% by weight of the antibody as determined by the Lowry method, e.g., greater than 99% by weight, (2) to a degree sufficient to obtain at least 15 residues of internal or N-terminus amino acid sequence by using a rotating cup sequencer, or (3) to homogeneity by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) under reducing or non-reducing conditions using Coomassie blue or silver staining.The isolated antibody includes the antibody in situ within recombinant cells, since at least one component of the antibody's natural environment will not be present. In some cases, the isolated antibody will be prepared through at least one purification step. The terms polypeptide, peptide, and protein, used interchangeably herein, refer to a polymeric form of amino acids of any length, which may include genetically encoded and non-genetically encoded amino acids, chemically or biochemically modified or derived amino acids, and polypeptides having modified peptide backbones. The term includes fusion proteins, which include, but are not limited to, fusion proteins with a heterologous amino acid sequence, fusions with heterologous and homologous leader sequences, with or without N-terminus methionine residues; immunologically tagged proteins; and the like. As used herein, the terms treatment, treat, and similar terms refer to achieving a desired pharmacological and / or physiological effect. The effect may be prophylactic in terms of totally or partially preventing a disease or a symptom thereof, and / or therapeutic in terms of a partial or complete cure of a disease and / or adverse effect attributable to the disease. Treatment, as used herein, covers any treatment of a disease in a mammal, particularly a human, and includes: (a) preventing the disease from occurring in a subject who may be predisposed to the disease but has not been diagnosed with it; (b) inhibiting the disease, i.e., halting its development; and (c) alleviating the disease, i.e., causing the disease to regress. The terms individual, subject, host, and patient, used interchangeably herein, refer to a mammal, including, but not limited to, murines (rats, mice), non-human primates, humans, canines, felines, ungulates (e.g., equines, bovines, ovines, porcines, caprines), etc. These terms also encompass any animal that has a complement system, such as mammals, fish, and some invertebrates. As such, these terms include mammals that possess a complement system, fish, and animals of UO3 company invertebrates, farm animals, working animals, zoo animals and laboratory animals. A therapeutically effective amount, or effective dose, refers to the quantity of an anti-complement antibody that, when administered to a mammal or other subject to treat a disease, is sufficient to effect the treatment. The therapeutically effective amount will vary depending on the specific anti-complement antibody, the disease and its severity, and the age, weight, etc., of the subject being treated. A biological sample encompasses a variety of sample types obtained from an individual and used in a diagnostic or monitoring assay. The definition includes blood and other liquid samples of biological origin, solid tissue samples such as biopsy specimens or tissue cultures, and cells derived from these and their progeny. The definition also includes samples that have been manipulated in any way after collection, such as through treatment with reagents, solubilization, or enrichment for certain components, such as polynucleotides. The term biological sample encompasses a clinical sample and also includes cultured cells, cell supernatants, used cells, serum, plasma, biological fluid, and tissue samples. The term biological sample includes urine, saliva, cerebrospinal fluid, interstitial fluid, ocular fluid, synovial fluid, blood fractions such as plasma and serum, and similar materials.The term biological sample also includes solid tissue samples, tissue culture samples, and cell samples. Before describing the present invention in further detail, it should be understood that this invention is not limited to the particular embodiments described, as these may obviously vary. It should also be understood that the terminology used herein is intended to describe only particular embodiments and is not meant to be exhaustive, since the scope of the present invention is limited only by the appended claims. Where a range of values ​​is provided, it shall be understood that each value involved, down to the tenth of a unit of the lower limit unless the context clearly establishes otherwise, between the upper and lower limits of that range and any other value established or involved in that established range, is included within the invention. The upper and lower limits of these smaller ranges may independently be included within the smaller ranges and are also included within the invention, subject to any limit specifically excluded in the established range. Where the established range includes one or both of the limits, the ranges excluding any or both included limits are also included in the invention. Unless otherwise indicated, all technical and scientific terms used herein have the same meaning commonly understood by a person skilled in the art to which the present invention pertains. While any method and material similar or equivalent to those described herein may also be used in the practice or testing of the present invention, the preferred methods and materials are described below. All publications mentioned herein are incorporated by reference to describe and describe the methods and / or materials in relation to which the publications are cited. It should be noted that, as used herein and in the appended claims, the singular forms a, an, and the include plural referents unless clearly indicated otherwise in the context. Thus, for example, the reference to a humanized anti-Cls antibody includes multiple such antibodies, and the reference to the framework region includes the reference to one or more framework regions and equivalents thereof known to the art, and so forth. It is further noted that the claims may be drafted to exclude any optional element. As such, this is intended as a basis for the use of exclusive terminology such as only, solely, and the like in relation to the enumeration of the elements of the claims or the use of a negative limitation. It is appreciated that certain features of the invention, which are described, for the sake of clarity, in the context of separate embodiments, can also be provided in combination in a single embodiment. Conversely, various features of the invention, which, for the sake of brevity, are described in the context of a single embodiment, can also be provided separately or in any suitable sub-combination. All combinations of the embodiments belonging to the invention are specifically included within the present invention and are described herein as if each combination were individually and specifically described. Furthermore, all sub-combinations of the various embodiments and elements thereof are also specifically included within the present invention and are described herein as if each sub-combination were individually and specifically described herein. The publications analyzed herein are provided solely by their description prior to the date UO3 of filing of this application. Nothing herein should be construed as an admission that this invention is not entitled to precede publication under the prior invention. In addition, the publication dates provided may differ from the actual publication dates, which may require individual confirmation. This description provides a humanized antibody that binds the complement protein Cls (i.e., a humanized anti-complement Cls antibody, also referred to herein as a humanized anti-Cls antibody, a humanized Cls antibody, and an antibody of this description) and a nucleic acid comprising a nucleotide sequence encoding such an antibody. This description also provides a composition comprising a humanized anti-Cls antibody of this description. This description provides methods for producing and using the antibodies, nucleic acids, and compositions of this description. This description provides methods for treating a complement-mediated disease or disorder, which involves administering a humanized anti-Cls antibody of this description. Anti-complement antibodies (Cls) This description provides humanized anti-complement Cls antibodies and pharmaceutical compositions comprising such antibodies. Complement Cls is an attractive target because it is located upstream in the complement cascade and has a narrow substrate specificity range. In some cases, an antibody that binds specifically to the activated form of Cls is of interest, for example, where the antibody does not bind substantially to the inactive form of Cls. An anti-Cls antibody of the present description is humanized, for example, one or more frame regions of the heavy chain variable region and / or the light chain variable region include sequences derived from a human immunoglobulin frame. In some cases, an anti-Cls antibody of the present description inhibits Cls-mediated cleavage of complement component C4, for example, by inhibiting the enzymatic activity of the serine protease domain of Cls. In some cases, an anti-Cls antibody of the present description inhibits Cls-mediated cleavage of complement component C2. In some cases, an anti-Cls antibody of the present description inhibits Cls-mediated cleavage of both C4 and C2. Humanizing a framework region reduces risk IVIA / a / ZUZZ / UU I UO3 of the antibody that elicits a human anti-mouse antibody (HAMA) response in humans. Methods recognized in the art for determining the immune response can be used to monitor an ARAM response in a particular patient or during clinical trials. Patients receiving humanized antibodies can be given an immunogenicity assessment at the start of and during therapy. The ARAM response is measured, for example, by detecting antibodies to the humanized therapeutic reagent in patient serum samples using a method known to a practitioner, including surface plasmon resonance technology (BIACORE) and / or enzyme-linked immunosorbent assay (ELISA). In many cases, a humanized anti-Cls antibody from a human subject does not substantially elicit an ARAM response in a human subject. Specific amino acids from the human variable frame region residues are selected for substitution based on their potential influence on CDR conformation and / or antigen binding. Unnatural juxtaposition of murine CDR regions with the human variable frame region can result in unnatural conformational constraints, which, unless corrected by substitution of specific amino acid residues, lead to a loss of binding affinity. The selection of amino acid residues for substitution can be determined, in part, by computer modeling. The computer hardware and software for producing three-dimensional images of immunoglobulin molecules are well-known in the field. In general, molecular models are produced starting from resolved structures for immunoglobulin chains or domains. The chains to be modeled are compared for amino acid sequence similarity with chains or domains in resolved three-dimensional structures, and the chains or domains showing the greatest sequence similarity are selected as starting points for molecular model construction. Chains or domains that share at least 50% sequence identity are selected for modeling; for example, those that share at least 60%, at least 70%, at least 80%, at least 90%, or more sequence identity are selected for modeling.The solved starting structures are modified to account for the differences between the actual amino acids in the modeled immunoglobulin chains or domains and those in the starting structure. The modified structures are then assembled into a composite immunoglobulin. Finally, the model is refined by minimizing energy and by verifying that all atoms are within appropriate distances from each other and that bond angles and lengths are within chemically acceptable limits. The frame and CDR regions are as defined by Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md., 1987 and 1991). An alternative structural definition has been proposed by Chothia et al., J. Mol. Biol. 196:901 (1987); Nature 342:878 (1989); and J. Mol. Biol. 186:651 (1989) (collectively referred to as Chothia). When frame residues, as defined by Kabat, supra, constitute structural loop residues defined by Chothia, supra, amino acids present in the mouse antibody can be selected for substitution in the humanized antibody.Residues adjacent to a CDR region include amino acid residues in positions immediately adjacent to one or more CDRs in the primary sequence of the humanized immunoglobulin chain, for example, in positions immediately adjacent to a CDR as defined by Kabat or a CDR as defined by Chothia (see, for example, Chothia and Lesk JMB 196:901 (1987)). These amino acids are particularly likely to interact with amino acids in the CDRs and, if selected from the acceptor, to distort the donor CDRs and reduce affinity. Furthermore, adjacent amino acids may interact directly with the antigen (Amit et al., Science, 233:747 (1986)), and selecting these amino acids from the donor may be desirable to maintain all antigen contacts that provide affinity in the original antibody. In some cases, a humanized anti-Cls antibody of the present description includes at least one humanized Vh frame region. In some cases, an anti-Cls antibody of the present description includes at least one humanized Vl frame region. In some cases, an anti-Cls antibody of the present description includes at least one humanized Vh frame region and at least one humanized Vl frame region. In some cases, a humanized anti-Cls antibody of the present description includes VL CDRs present in the following amino acid sequence: DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKTGQPPKILIYDASNLESG IPARFSGSGSGTDFTLNIHPVEEEDAAIYYCQQSNEDPWTFGGGTKLEIK (SEQ ID NO:7). In some cases, a humanized anti-Cls antibody of the present description includes VH CDRs present in the following amino acid sequence: EVQLQQSGAELVRPGASVKLSCTASGFNIKDDYIHWVKQRPEQGLEWIGRIDPADGHTKYA PKFQVKATITADTSSNTAYLQLSSLTSEDTAVYYCARYGYGREVFDYWGQGTTLTVSS (SEQ ID NO:8). In some cases, a humanized anti-Cls antibody of the present description includes VL CDRs present in SEQ ID NO: 7 and VH CDRs present in SEQ ID NO:8. VL CDR1 (CDR-L1): SEQ ID NO:1: KASQSVDYDGDSYMN VL CDR2 (CDR-L2): SEQ ID NO:2: DASNLES VL CDR3 (CDR-L3): SEQ ID NO:3: QQSNEDPWT VH CDR1 (CDR-H1): SEQ ID NO:4: DDYIH VH CDR2 (CDR-H2): SEQ ID NO:5: RIDPADGHTKYAPKFQV VH CDR3 (CDR-H3) : SEQ ID NO:6: YGYGREVFDY In some cases, a humanized anti-Cls antibody of the present description comprises a light chain variable region comprising the amino acid sequences of CDR SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3 (CDR-L1, CDR-L2, and CDR-L3, respectively). In some embodiments, an anti-Cls antibody of the present description comprises a heavy chain variable region comprising the amino acid sequences of CDR SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 (CDR-H1, CDR-H2, and CDRH3, respectively). In some cases, a humanized anti-Cls antibody of the present description comprises a VH region comprising the following sequence: (Q / E)VQL(V / Q)QSGAE(V / L)KKPGASVK(L / V)SC(T / A)ASGFNIKDDYIH WV(K / R)QAPGQGLEWIGRIDPADGHTKYAPKFQVK(V / A)TITADTST(S / N)TAY(L / M )(E / Q)LSSL(R / T)SEDTAVYYCARYGYGREVFDYWGQGTTVTVSS (SEQ ID NO: 2 6) . In some cases, a humanized anti-Cls antibody of the present description comprises a VH region comprising an amino acid sequence that has at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity with the sequence of UO3 amino acids described in FIGURE 1, and established in SEQ ID NO: 10, where amino acid 1 is Glu, amino acid 5 is Val, amino acid 11 is Leu, amino acid 12 is Lys, amino acid 13 is Lys, amino acid 20 is Leu, amino acid 23 is Thr, amino acid 38 is Lys, amino acid 40 is Ala, amino acid 42 is Gly, amino acid 67 is Ala, amino acid 75 is Thr, amino acid 76 is Asn, amino acid 80 is Leu, amino acid 81 is Gln, amino acid 83 is Thr, and amino acid 109 is Val, where the numbering of the amino acids is as described in FIGURE 1. In some cases, a humanized anti-Cls antibody of the present description comprises a VH region comprising the amino acid sequence described in FIGURE 1 and established in SEQ ID NO:10. In some cases, a humanized anti-Cls antibody of the present description comprises a VH region comprising an amino acid sequence having at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity with the amino acid sequence described in FIGURE 2 and stated in SEQ ID NO: 12, wherein amino acid 1 is Glu, amino acid 5 is Val, amino acid 11 is Val, amino acid 12 is Lys, amino acid 13 is Lys, amino acid 20 is Leu, amino acid 23 is Thr, amino acid 38 is Lys, amino acid 40 is Ala, amino acid 42 is Gly, amino acid 67 is Ala, the UO3 amino acid 75 is Thr, amino acid 76 is Asn, amino acid 80 is Leu, amino acid 81 is Glu, amino acid 83 is Arg, and amino acid 109 is Val, where the numbering of the amino acids is as described in FIGURE 2. In some cases, a humanized anti-Cls antibody of the present description comprises a VH region comprising the amino acid sequence described in FIGURE 2 and established in SEQ ID NO:12. In some cases, a humanized anti-Cls antibody of the present description comprises a VH region comprising an amino acid sequence having at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity with the amino acid sequence described in FIGURE 3 and established in SEQ ID NO: 14, wherein amino acid 1 is Gln, amino acid 5 is Val, amino acid 11 is Val, amino acid 12 is Lys, amino acid 13 is Lys, amino acid 20 is Leu, amino acid 23 is Thr, amino acid 38 is Lys, amino acid 40 is Ala, amino acid 42 is Gly, amino acid 67 is Val, amino acid 75 is Thr, amino acid 76 is Ser, amino acid 80 is Leu, amino acid 81 is Glu, amino acid 83 is Arg, and Amino acid 109 is Val, where the numbering of the amino acids is as described in FIGURE 3. In some cases, a humanized anti-Cls antibody of the present description comprises a VH region comprising the amino acid sequence described in FIGURE 3 and established in SEQ ID NO:14. In some cases, a humanized anti-Cls antibody of the present description comprises a VH region comprising an amino acid sequence having at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity with the amino acid sequence described in FIGURE 4 and established in SEQ ID NO: 16, wherein amino acid 1 is Gln, amino acid 5 is Val, amino acid 11 is Val, amino acid 12 is Lys, amino acid 13 is Lys, amino acid 20 is Val, amino acid 23 is Thr, amino acid 38 is Arg, amino acid 40 is Ala, amino acid 42 is Gly, amino acid 67 is Val, amino acid 75 is Thr, amino acid 76 is Ser, amino acid 80 is Met, amino acid 81 is Glu, amino acid 83 is Arg, and the amino acid 109 is Val, where the numbering of the amino acids is as described in FIGURE 4. In some cases, a humanized anti-Cls antibody of the present description comprises a VH region comprising the amino acid sequence described in FIGURE 4 and established in SEQ ID NO:16. In some cases, a humanized anti-Cls antibody of the present description comprises a VH region comprising an amino acid sequence having at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity with the amino acid sequence described in FIGURE 5 and established in SEQ ID NO: 18, wherein amino acid 1 is Gln, amino acid 5 is Val, amino acid 11 is Val, amino acid 12 is Lys, amino acid 13 is Lys, amino acid 20 is Val, amino acid 23 is Ala, amino acid 38 is Arg, amino acid 40 is Ala, amino acid 42 is Gly, amino acid 67 is Val, amino acid 75 is Thr, amino acid 76 is Ser, amino acid 80 is Met, amino acid 81 is Glu, amino acid 83 is Arg, and amino acid 109 is Val, where the numbering of the amino acids is as described in FIGURE 5. In some cases, a humanized anti-Cls antibody of the present description comprises a VH region comprising the amino acid sequence described in FIGURE 5 and established in SEQ ID NO:18. In some cases, a humanized anti-Cls antibody of the present description comprises a VL region comprising the following sequence: DIVLTQSPDSLAVSLGERATISCKASQSVDYDGDSYMNWYQQK(T / P)GQPPK(I / L)LIYDASNLESGIPARFSGSGSGTDFTLTISSLE(E / P)EDFA (I / V)YYCQQSNEDPW TFGGGTKVEIK (SEQ ID NO:27). In some cases, a humanized anti-Cls antibody of the present description comprises a VL region comprising an amino acid sequence having at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity with the amino acid sequence described in FIGURE 6 and stated in SEQ ID NO: 20, wherein amino acid 9 is Asp, amino acid 17 is Glu, amino acid 40 is Thr, amino acid 46 is lie, amino acid 74 is Thr, amino acid 76 is Ser, amino acid 77 is Ser, amino acid 78 is Leu, amino acid 80 is Glu, amino acid 83 is Phe, amino acid 85 is lie, and amino acid 104 is Val, wherein the numbering of the amino acids is as described in FIGURE 6. In some cases, a humanized anti-Cls antibody of the present description comprises a VL region comprising the amino acid sequence described in FIGURE 6 and established in SEQ ID NO:20. In some cases, a humanized anti-Cls antibody of the present description comprises a VL region comprising an amino acid sequence having at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity with the amino acid sequence described in FIGURE 7 and stated in SEQ ID NO: 22, wherein amino acid 9 is Asp, amino acid 17 is Glu, amino acid 40 is Pro, amino acid 46 is lie, amino acid 74 is Thr, amino acid 76 is Ser, amino acid 77 is Ser, amino acid 78 is Leu, amino acid 80 is Pro, amino acid 83 is Phe, amino acid 85 is lie, and amino acid 104 is Val, wherein the numbering of the amino acids is as described in FIGURE 7. In some cases, a humanized anti-Cls antibody of the present description comprises a VL region comprising the amino acid sequence described in FIGURE 7 and established in SEQ ID NO:22. In some cases, a humanized anti-Cls antibody of the present description comprises a VL region comprising an amino acid sequence having at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity with the amino acid sequence described in FIGURE 8 and stated in SEQ ID NO: 24, wherein amino acid 9 is Asp, amino acid 17 is Glu, amino acid 40 is Pro, amino acid 46 is Leu, amino acid 74 is Thr, amino acid 76 is Ser, amino acid 77 is Ser, amino acid 78 is Leu, amino acid 80 is Pro, amino acid 83 is Phe, amino acid 85 is Val, and amino acid 104 is Val, wherein the numbering of the amino acids is as described in FIGURE 8. In some cases, a humanized anti-Cls antibody of the present description comprises a VL region comprising the amino acid sequence described in FIGURE 8 and established in SEQ ID NO:24. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 1 amino acid sequence described in FIGURE 1 and such UO3 as stated in SEQ ID NO: 10; and b) a variant 1 amino acid sequence of VL described in FIGURE 6 and as stated in SEQ ID NO: 20. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 1 amino acid sequence described in FIGURE 1 and as set out in SEQ ID NO: 10; and b) a VL variant 2 amino acid sequence described in FIGURE 7 and as set out in SEQ ID NO: 22. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 1 amino acid sequence described in FIGURE 1 and as set out in SEQ ID NO: 10; and b) a VL variant 5 amino acid sequence described in FIGURE 8 and as set out in SEQ ID NO: 24. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 2 amino acid sequence described in FIGURE 2 and as set out in SEQ ID NO: 12; and b) a VL variant 1 amino acid sequence described in FIGURE 6 and as set out in SEQ ID NO: 20. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 2 amino acid sequence described in FIGURE 2 and as set out in SEQ ID NO: 12; and b) a VL variant 2 amino acid sequence described in FIGURE 7 and as set out in SEQ ID NO: 22. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 2 amino acid sequence described in FIGURE 2 and as set out in SEQ ID NO: 12; and b) a VL variant 5 amino acid sequence described in FIGURE 8 and as set out in SEQ ID NO: 24. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 3 amino acid sequence described in FIGURE 3 and as set out in SEQ ID NO: 14; and b) a VL variant 1 amino acid sequence described in FIGURE 6 and as set out in SEQ ID NO: 20. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 3 amino acid sequence described in FIGURE 3 and as set out in SEQ ID NO: 14; and b) a VL variant 2 amino acid sequence described in FIGURE 7 and set out in SEQ ID NO: 22. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 3 amino acid sequence described in FIGURE 3 and as set out in SEQ ID NO: 14; and b) a VL variant 5 amino acid sequence described in FIGURE 8 and as UO3 as set out in SEQ ID NO: 24. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 4 amino acid sequence described in FIGURE 4 and as set out in SEQ ID NO: 16; and b) a VL variant 1 amino acid sequence described in FIGURE 6 and as set out in SEQ ID NO: 20. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 4 amino acid sequence described in FIGURE 4 and as set out in SEQ ID NO: 16; and b) a VL variant 2 amino acid sequence described in FIGURE 7 and as set out in SEQ ID NO: 22. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 4 amino acid sequence described in FIGURE 4 and as set out in SEQ ID NO: 16; and b) a VL variant 5 amino acid sequence described in FIGURE 8 and as set out in SEQ ID NO: 24. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 5 amino acid sequence described in FIGURE 5 and as set out in SEQ ID NO: 18; and b) a VL variant 1 amino acid sequence described in FIGURE 6 and as ΜΛ / a / ZUZZ / UU I UO3 as set forth in SEQ ID NO:20. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 5 amino acid sequence described in FIGURE 5 and as set out in SEQ ID NO: 18; and b) a VL variant 2 amino acid sequence described in FIGURE 7 and as set out in SEQ ID NO: 22. In some cases, a humanized anti-Cls antibody of the present description comprises: a) a VH variant 5 amino acid sequence described in FIGURE 5 and as set out in SEQ ID NO: 18; and b) a VL variant 5 amino acid sequence described in FIGURE 8 and as set out in SEQ ID NO: 24. In some embodiments, a humanized anti-Cls antibody of the present description binds a complement protein Cls from an individual possessing a complement system. In some embodiments, a humanized anti-Cls antibody of the present description binds a complement protein Cls from a mammal, fish, or invertebrate possessing a complement system. In some embodiments, a humanized anti-Cls antibody of the present description binds a mammalian complement protein Cls. In some embodiments, a humanized anti-Cls antibody of the present description binds a human complement protein Cls. In some embodiments, a humanized anti-Cls antibody of the present description binds a rat complement protein Cls. In some embodiments, a humanized anti-Cls antibody of the present description binds a complement protein Cls having the amino acid sequence described in FIGURE 13 (SEQ ID NO: 9).The amino acid sequence SEQ ID NO: 9 represents the Cls protein of the Homo sapiens complement that has the amino acid sequence established in FIGURE 13. In some embodiments, a humanized anti-Cls antibody of the present description binds a complement protein Cls with a dissociation constant (Kd) of no more than 2.5 nM. In some embodiments, a humanized anti-Cls antibody of the present description binds a complement protein Cls with a Kd of no more than 2 nM. In some embodiments, a humanized anti-Cls antibody of the present description binds a complement protein Cls with a Kd of no more than 1 nM. In some embodiments, a humanized anti-Cls antibody of the present description binds a Cls complement protein with a Kd of no more than 0.9 nM, no more than 0.8 nM, no more than 0.7 nM, no more than 0.6 nM, no more than 0.5 nM, no more than 0.4 nM, no more than 0.3 nM, no more than 0.2 nM, no more than 0.1 nM. In some embodiments, a humanized anti-Cls antibody of the present description binds a Cls complement protein with a Kd of no more than 0.3 nM.In some embodiments, a humanized anti-Cls antibody of the present description binds a complement protein Cls with a Kd of no more than 0.2 nM. In some embodiments, a humanized anti-Cls antibody of the present description binds a complement protein Cls with a Kd of no more than 0.1 nM. The methods for measuring the binding of an antibody to the Cls protein can be determined by a person skilled in the technique. In some embodiments, a humanized anti-Cls antibody of the present description binds a complement Cls protein with a Kd of no more than 90 pM, no more than 80 pM, no more than 70 pM, no more than 60 pM, no more than 50 pM, no more than 40 pM, no more than 30 pM, no more than 20 pM, no more than 10 pM, no more than 9 pM, no more than 8 pM, no more than 7 pM, no more than 6 pM, no more than 5 pM, no more than 4 pM, no more than 3 pM, no more than 2 pM, no more than 1 pM. In some embodiments, a humanized anti-Cls antibody of the present description binds a human complement protein Cls with a dissociation constant (Kd) of no more than 2.5 nM. In some embodiments, a humanized anti-Cls antibody of the present description binds a human complement protein Cls with a Kd of no more than 2 nM. In some embodiments, a humanized anti-Cls antibody of the present description binds a human complement protein Cls with a Kd of no more than 1 nM. In some embodiments, a humanized anti-Cls antibody of the present description binds a human complement protein Cls with a Kd of no more than 0.9 nM, no more than 0.8 nM, no more than 0.7 nM, no more than 0.6 nM, not more than 0.5 nM, not more than 0.4 nM, not more than 0.3 nM, not more than 0.2 nM, not more than 0.1 nM. In some embodiments, a humanized anti-Cls antibody of the present description binds a human complement protein Cls with a KD of not more than 0.3 nM. In some embodiments, a humanized anti-Cls antibody of the present description binds a human complement protein Cls with a KD of not more than 0.2 nM. In some embodiments, a humanized anti-Cls antibody of the present description binds a human complement protein Cls with a KD of not more than 0.1 nM. The methods for measuring the binding of an antibody to the human Cls protein may be determined by a person skilled in the art. In some modalities, a binding assay such as described in the Examples is used to determine the Kd between an antibody and a human Cls protein. In some embodiments, a humanized anti-Cls antibody of the present description binds a human complement protein Cls with a Kd of no more than 90 pM, no more than 80 pM, no more than 70 pM, no more than 60 pM, no more than 50 pM, no more than 40 pM, no more than 30 pM, no more than 20 pM, no more than 10 pM, no more than 9 pM, no more than 8 pM, no more than 7 pM, no more than 6 pM, no more than 5 pM, no more than 4 pM, no more than 3 pM, no more than 2 pM, no more than 1 pM. In some forms, a humanized anti-Cls antibody of the present description inhibits the classical complement pathway with a mean maximum inhibitory concentration (ICso) of 10“8M or less, 5 x 10-9M or less, or 10“9M or less. Nucleic acids, expression vectors, and host cells This description provides a nucleic acid comprising a nucleotide sequence encoding a humanized anti-Cls antibody of this description. In some cases, a nucleic acid of this description comprises a nucleotide sequence encoding the VH region of a humanized anti-Cls antibody of this description. In some cases, a nucleic acid of this description comprises a nucleotide sequence encoding the VL region of a humanized anti-Cls antibody of this description. In some cases, a nucleic acid of this description comprises a nucleotide sequence encoding both the VH and VL regions of the humanized anti-Cls antibody of this description. A nucleotide sequence encoding a humanized anti-Cls antibody of the present description may be operatively linked to one or more regulatory elements, such as a promoter and enhancer, that allow expression of the nucleotide sequence in the intended target cells (e.g., a cell that is genetically modified to synthesize the encoded antibody). Therefore, in some cases, the present description provides a nucleic acid comprising a nucleotide sequence encoding a humanized anti-Cls antibody of the present description, wherein the nucleotide sequence is operatively linked to one or more regulatory elements, e.g., a promoter and / or an enhancer. Promoter and enhancer elements are known in the technique. Promoters suitable for use in prokaryotic host cells include, but are not limited to, a bacteriophage T7 RNA polymerase promoter; a T3 promoter; a T5 promoter; a lambda P promoter; a trp promoter; a lac operon promoter; a hybrid promoter, for example, a lac / tac hybrid promoter, a tac / trc hybrid promoter, a trp / lac promoter, a T7 / lac promoter; a trc promoter; a tac promoter, and the like; a gpt promoter; and an araBAD promoter. in vivo regulated promoters, such as an ssaG promoter or related promoter (see, for example, U.S. Patent Publication No. 20040131637), a pagC promoter (Pulkkinen and Miller, J. Bacteriol., 1991: 173(1): 86-93; Alpuche-Aranda et al., PNAS, 1992; 89(21): 10079-83), a nirB promoter (Harborne et al. (1992) Mol. Micro. 6:2805-2813), and the like (see, for example, Dunstan et al. (1999) Infect. Immun.67:5133-5141; McKelvie et al. (2004) Vaccine 22:32 43-32 55; and Chatfield et al. (1992) Biotechnol. 10:888-892); a sigma70 promoter, for example, a sigma70 consensus promoter (see, for example, GenBank accession numbers AX798980, AX798961 and AX798183); a stationary-phase promoter, for example, a dps promoter, an spv promoter and the like; a promoter derived from the SPI-2 pathogenicity island (see, for example, WO96 / 17951); an actA promoter (see, for example, Shetron-Rama et al. (2002) Infect. Immun. 70:1087-1096); an rpsM promoter (see, for example, Valdivia and Falkow (1996). Mol. Microbiol. 22:367); a tet promoter (see, for example, Hállen,W. and Wissmann, A. (1989) In Saenger,W. and Heinemann, U. (eds), Topics in Molecular and Structural Biology, Protein-Nucleic Acid Interaction. Macmillan, London, UK, vol. 10, pp. 143-162); an SP6r promoter (see, for example, Melton et al. (1984) Nuci. Acids Res. 12:7035); and the like.Strong promoters suitable for use in prokaryotes such as Escherichia coli include, but are not limited to, Trc, Tac, T5, T7, and Piambda. Non-exhaustive examples of operators for use in bacterial host cells include a lactose promoter operator (the LacI repressor protein changes conformation upon contact with lactose, thereby preventing the LacI repressor protein from binding to the operator), a tryptophan promoter operator (when complexed with tryptophan, the TrpR repressor protein has a conformation that binds to the operator; in the absence of tryptophan, the TrpR repressor protein has a conformation that does not bind to the operator), and a tac promoter operator (see, for example, deBoer et al. (1983) Proc. Nati. Acad. Sci. EUA 80:21-25). In some modalities, for example, for expression in a yeast cell, a suitable promoter is a constitutive promoter such as an ADH1 promoter, a PGK1 promoter, an ENO promoter, a PYK1 promoter and the like; or a tunable promoter such as a GAL1 promoter, a GALIO promoter, an ADH2 promoter, a PHO5 promoter, a CUP1 promoter, a GAL7 promoter, a MET25 promoter, a MET3 promoter, a CYC1 promoter, a HIS3 promoter, an ADH1 promoter, a PGK promoter, a GAPDH promoter, an ADC1 promoter, a TRP1 promoter, a URA3 promoter, a LEU2 promoter, an ENO promoter, a TP1 promoter and AOX1 promoters (for example, for use in Pichia). For expression in a eukaryotic cell, suitable promoters include, but are not limited to, enhancer elements and promoters of the immunoglobulin heavy and / or light chain gene; the cytomegalovirus immediate early promoter; the herpes simplex thymidine kinase promoter; the SV40 early and late promoters; the promoter present in retrovirus long terminal repeats; the mouse metallothionein I promoter; and several tissue-specific promoters known in the technique. Selecting the appropriate vector and promoter is within the level of an expert in the technique. The nucleic acid comprising a nucleotide sequence encoding a humanized anti-Cls antibody of the present description may be present in an expression vector and / or a cloning vector. The present description provides a recombinant vector comprising a nucleic acid comprising a nucleotide sequence encoding a humanized anti-Cls antibody of the present description, wherein the recombinant vector is a cloning vector. The present description provides a recombinant vector comprising a nucleic acid comprising a nucleotide sequence encoding a humanized anti-Cls antibody of the present description, wherein the recombinant vector is an expression vector, for example, wherein the nucleotide sequence is operatively linked to the appropriate regulatory sequences in the expression vector of the encoded antibody.Where an antibody herein comprises two separate polypeptides, the nucleic acids encoding the two polypeptides may be cloned into identical or separate vectors to form one or more recombinant vectors. A recombinant vector may include a selectable marker, an origin of replication, and other features that provide for replication and / or maintenance of the recombinant vector (e.g., recombinant expression vector). Experts in the technique are familiar with a large number of suitable vectors and promoters; many are commercially available for generating a recombinant vector of this type. The following vectors are provided as examples. Bacterial: pBs, phagescript, PsiX174, pBluescript SK, pBs KS, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene, La Jolla, Calif., USA); pTrc99A, pKK223-3, pKK233-3, pDR540, and pRIT5 (Pharmacia, Uppsala, Sweden). Eukaryotic: pWLneo, pSV2cat, pOG44, PXR1, pSG (Stratagene); pSVK3, pBPV, pMSG, and pSVL (Pharmacia). Expression vectors generally have convenient restriction sites located near the promoter sequence to allow the insertion of nucleic acid sequences encoding heterologous proteins. A selectable marker that functions in the expression host may be present. Suitable expression vectors include, but are not limited to, viral vectors. Examples of viral vectors include, but are not limited to, viral vectors based on: vaccinia virus; poliovirus; adenovirus (see, for example, Li et al., Invest Opthalmol Vis Sci 35:2543-2549, 1994; Borras et al., Gene Ther 6:515 524, 1999; Li and Davidson, PNAS 92:7700-7704, 1995; Sakamoto et al., H Gene Ther 5:1088 1097, 1999; WO 94 / 12649, WO 93 / 03769; 93 / 19191; WO 94 / 28938; WO 95 / 11984 and WO 95 / 00655); adeno-associated virus (see, for example, Ali et al., Hum Gene Ther 9:81 86, 1998, Flannery et al., PNAS 94:6916 6921, 1997; Bennett et al., Invest Opthalmol Vis Sci 38:2857 2863, 1997; Jomary et al., Gene Ther 4:683 690, 1997, Rolling et al., Hum Gene Ther 10:641 648, 1999; Hum Mol Genet 5:591 594, 1996; 63:3822-382 8; Mendelson et al. Virol. (1988) 166:154-165; and Flotte et al., PNAS (1993) 90:10613-10617); SV40; herpes simplex virus; a retroviral vector (e.g., murine leukemia virus, splenic necrosis virus, and retrovirus-derived vectors such as Rous sarcoma virus, Harvey sarcoma virus, avian leukosis virus, human immunodeficiency virus (see, e.g., Miyoshi et al., PNAS 94:10319 23, 1997; Takahashi et al., J Virol 73:7812 7816, 1999), myeloproliferative sarcoma virus, and mammary tumor virus); and similar viruses. Host cells This description provides genetically modified, isolated host cells (e.g., in vitro cells) that are genetically modified with a nucleic acid of the present. In some embodiments, a genetically modified host cell isolated from the subject can produce an antibody of the subject. UO3 refers to such a cell as a recombinant cell or a genetically modified host cell. A genetically modified host cell of the present description comprises a nucleic acid comprising a nucleotide sequence encoding a humanized anti-Cls antibody of the present description. Suitable host cells include eukaryotic host cells, such as mammalian, insect, or yeast cells; and prokaryotic cells, such as bacterial cells. The introduction of a nucleic acid from the host cell can be accomplished, for example, by calcium phosphate precipitation, DEAE-mediated dextran transfection, liposome-mediated transfection, electroporation, or other known methods. Suitable mammalian cells include primary cells and immortalized cell lines. Mammalian cell lines include human cell lines, non-human primate cell lines, rodent cell lines (e.g., mouse, rat), and similar cells. Suitable mammalian cell lines include, but are not limited to, HeLa cells (e.g., American Type Culture Collection (ATCC) No. CCL-2), CHO cells (e.g., ATCC No. CRL9618, CCL61, CRL9096), 293 cells (e.g., ATCC No. CRL-1573), Vero cells, NIH 3T3 cells (e.g., ATCC No. CRL-1658), Huh-7 cells, BHK cells (e.g., ATCC No. CCL10), PC12 cells (ATCC No. CRL1721), COS cells, COS-7 cells (ATCC No. CRL1651), RAT1 cells, mouse L cells (ATCC No. CCLI.3), human embryonic kidney (HEK) cells (ATCC No. CRL1573), cells HLHepG2 and similar cells. In some cases, the cells are HEK cells.In some cases, the cells are CHO cells, for example, CHO-K1 cells (ATCC No. CCL-61), CHO-M cells, CHO-DG44 cells (ATCC No. PTA-3356), and the like. In some modalities, the host cell is a COS cell. In some modalities, the host cell is a 293 cell. In some modalities, the host cell is a CHO cell. Suitable yeast cells include, but are not limited to, Pichia pastoris, Pichia finlandica, Pichia trehalophila, Pichia koclamae, Pichia membranaefaciens, Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia sp. , Saccharomyces cerevisiae, Saccharomyces sp. , Hansenula polymorpha, Kluyveromyces sp. , Kluyveromyces lactis, Candida albicans, Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Trichoderma reesei, Chrysosporium lucknowense, Fusarium sp. , Fusarium gramineum, Fusarium venenatum, Neurospora crassa, Chlamydomonas reinhardtii, and the like. In some embodiments, the host cell is a Saccharomyces. In some embodiments, the host cell is a Pichia Suitable prokaryotic cells include, but are not limited to, any of a variety of laboratory strains of Escherichia coli, B. subtilis, Lactobacillus sp., and the like. See, for example, Carrier et al. (1992) J. Immunol. 14(8):1176–1181; U.S. Patent No. 6,447,784; and Sizemore et al. (1995) Science 270:299–302. Typically, the laboratory strain is nonpathogenic. In some forms, the host cell is Escherichia coli. In some forms, the host cell is B. subtilis. Pharmaceutical compositions This description provides compositions, including pharmaceutical compositions, comprising a humanized anti-Cls antibody of this description. In general, a pharmaceutical composition, also referred to herein as a formulation, comprises an effective amount of a humanized anti-Cls antibody of this description. An effective amount means a dosage sufficient to produce a desired result, for example, a reduction in an adverse symptom associated with a complement-mediated disease or disorder, improvement of a symptom of a complement-mediated disease or disorder, slowing of the progression of a complement-mediated disease or disorder, etc. Generally, the desired result is at least a reduction in a symptom of a complement-mediated disease or disorder, compared to a control.In some embodiments, a humanized anti-Cls antibody of the present description is formulated and / or modified to allow the antibody to cross the blood-brain barrier. In some embodiments, a humanized anti-Cls antibody of the present description is administered in a manner that bypasses the blood-brain barrier. In some embodiments, a humanized anti-Cls antibody of the present description is formulated with an agent that facilitates crossing the blood-brain barrier. In some embodiments, a humanized anti-Cls antibody of the present description is fused, directly or via a linker, to a compound that promotes crossing the blood-brain barrier. Formulations In the methods described herein, a humanized anti-Cls antibody of the present description can be administered to the host using any convenient means that can result in the desired therapeutic or diagnostic effect. Therefore, the agent can be incorporated into a variety of formulations for therapeutic administration. More particularly, a humanized anti-Cls antibody of the present description can be formulated into pharmaceutical compositions by combining it with carriers. Pharmaceutically acceptable UO3, appropriate pharmaceutically acceptable diluents, or other pharmaceutically acceptable excipients, and may be formulated in solid, semi-solid, liquid, or gaseous preparations, such as tablets, capsules, powders, granules, ointments, solutions, suppositories, injections, inhalers, and aerosols. In some embodiments, a pharmaceutical composition comprises a humanized anti-Cls antibody of the present description and a pharmaceutically acceptable excipient. In pharmaceutical dosage forms, the humanized anti-Cls antibody described herein may be administered as its pharmaceutically acceptable salts, or may be used alone or in appropriate combination with other pharmaceutically active compounds. The following methods and excipient are merely illustrative and are not exhaustive. For oral preparations, a humanized anti-Cls antibody of the present description may be used alone or in combination with suitable additives to make tablets, powders, granules or capsules, for example, with conventional additives such as lactose, mannitol, corn starch or potato starch; with binders such as crystalline cellulose, cellulose derivatives, acacia, corn starch, potato starch or gelatins; with disintegrants such as corn starch or sodium carboxymethylcellulose; with lubricants such as talc or magnesium stearate; and if desired, with diluents, buffering agents, wetting agents, preservatives and flavoring agents. A humanized anti-Cls antibody of the present description may be formulated into injection preparations by dissolving, suspending, or emulsifying the antibody in an aqueous or non-aqueous solvent, such as vegetable or other similar oils, propylene glycol, synthetic aliphatic acid glycerides, injectable organic esters (e.g., ethyl oleate), esters of higher aliphatic acids, or propylene glycol, and, if desired, with conventional additives such as solubilizers, isotonic agents, suspending agents, emulsifying agents, stabilizers, and preservatives. Parenteral vehicles include sodium chloride solution, Ringer's dextrose, sodium chloride and dextrose, Ringer's lactic solution, or fixed oils. Intravenous vehicles include fluid and nutrient regenerators, electrolyte regenerators (such as those based on Ringer's dextrose), and the like.Furthermore, the pharmaceutical composition of the present description may include additional agents such as dopamine or psychopharmacological drugs, depending on the intended use of the pharmaceutical composition. Pharmaceutical compositions comprising a humanized anti-Cls antibody of the present description are prepared by mixing a humanized anti-Cls antibody of the present description having the desired degree of purity with optional physiologically acceptable carriers, other excipients, stabilizers, surfactants, buffers, and / or tonicity agents. The acceptable carriers, other excipients, and / or stabilizers are non-toxic to the intended users at the dosages and concentrations employed and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid, glutathione, cysteine, methionine, and citric acid; preservatives (such as ethanol, benzyl alcohol, phenol, m-cresol, p-chloro-m-cresol, methyl or propyl parabens, benzalkonium chloride, or combinations thereof);amino acids such as arginine, glycine, ornithine, lysine, histidine, glutamic acid, aspartic acid, isoleucine, leucine, alanine, phenylalanine, tyrosine, tryptophan, methionine, serine, proline and combinations thereof; monosaccharides, disaccharides and other carbohydrates; low molecular weight polypeptides (less than about 10 residues); proteins, such as serum albumin or gelatin; chelating agents such as EDTA; sugars such as trehalose, sucrose, lactose, glucose, mannose, maltose, galactose, fructose, sorbose, raffinose, glucosamine, N61 methylglucosamine, galactosamine and neuraminic acid; and / or non-ionic surfactants such as Tween, Brij Pluronics, Triton-X or polyethylene glycol (PEG). The pharmaceutical composition may be in liquid form, lyophilized form, or liquid form reconstituted from a lyophilized form, where the lyophilized preparation is reconstituted with a sterile solution prior to administration. The standard procedure for reconstituting a lyophilized composition is to add back a volume of pure water (typically equivalent to the volume removed during lyophilization); however, solutions comprising antibacterial agents may be used for the production of pharmaceutical compositions for parenteral administration; see also Chen (1992) Drug Dev Ind Pharm 18, 1311-54. The concentrations of example antibodies in a pharmaceutical composition of the present may range from about 1 mg / mL to about 200 mg / mL or from about 50 mg / mL to about 200 mg / mL, or from about 150 mg / mL to about 200 mg / mL. An aqueous formulation of a humanized anti-Cls antibody of the present description can be prepared in a buffered solution with pH, ​​for example, a pH ranging from about 4.0 to about 7.0, or from about 5.0 to about 6.0, or alternatively IVIA / a / ZUZZ / UU I UO3 around 5.5. Examples of buffers suitable for a pH within this range include phosphate, histidine, citrate, succinate, acetate, and other organic acid buffers. The buffer concentration can range from around 1 mM to around 100 mM or from around 5 mM to around 50 mM, depending, for example, on the buffer and the desired tonicity of the formulation. A tonicity agent can be included in the antibody formulation to modulate its tonicity. Examples of tonicity agents include sodium chloride, potassium chloride, glycerin, and any component of the amino acid group, sugars, or combinations thereof. In some formulations, the aqueous formulation is isotonic, although hypertonic or hypotonic solutions may be suitable. The term isotonic denotes a solution that has the same tonicity as another solution to which it is compared, such as physiological saline or serum. Tonicity agents can be used in concentrations ranging from approximately 5 mM to approximately 350 mM, for example, from 100 mM to 350 nM. A surfactant can also be added to the antibody formulation to reduce aggregation of the formulated antibody and / or minimize particle formation in the formulation and / or reduce absorption. Example surfactants include polyoxyethylene sorbitan fatty acid esters (Tween), polyoxyethylene alkyl ethers (Brij), alkylphenyl polyoxyethylene ethers (Triton-X), polyoxyethylene-polyoxypropylene copolymer (Poloxamer, Pluronic), and sodium dodecyl sulfate (SDS). Examples of suitable polyoxyethylene sorbitan fatty acid esters are polysorbate 20 (sold under the trade name Tween 20™) and polysorbate 80 (sold under the trade name Tween 80™). Examples of suitable polyethylene-polypropylene copolymers are those sold under the names Pluronic® F68 or Poloxamer 188™. Examples of suitable polyoxyethylene alkyl ethers are those sold under the trade name Brij™.Example surfactant concentrations can range from around 0.001% to around 1% w / v. A lyoprotectant can also be added to protect the labile active ingredient (e.g., a protein) against destabilizing conditions during the freeze-drying process. Examples of known lyoprotectants include sugars (such as glucose and sucrose); polyols (such as mannitol, sorbitol, and glycerol); and amino acids (such as alanine, glycine, and glutamic acid). Lyoprotectants can be included in concentrations ranging from approximately 10 nM to 500 nM. In some embodiments, a formulation of the present includes a humanized anti-Cls antibody of the present description, and one or more of the agents identified above (e.g., a surfactant, a buffer, a stabilizer, a tonicity agent) and is essentially free of one or more preservatives, such as ethanol, benzyl alcohol, phenol, m-cresol, p-chloro-m-cresol, methyl or propyl parabens, benzalkonium chloride, and combinations thereof. In other embodiments, a preservative is included in the formulation, for example, at concentrations ranging from about 0.001 to about 2% (w / v). For example, a formulation of the present may be a liquid or lyophilized formulation suitable for parenteral administration, and may comprise: about 1 mg / mL to about 200 mg / mL of a humanized anti-Cls antibody of the present description; about 0.001% to about 1% of at least one surfactant; about 1 mM to about 100 mM of a buffer; optionally about 10 mM to about 500 mM of a stabilizer; and about 5 mM to about 305 mM of a tonicity agent; and has a pH of about 4.0 to about 7.0. As another example, a parenteral formulation of the present is a liquid or lyophilized formulation comprising: about 1 mg / mL to about 200 mg / mL of a humanized anti-Cls antibody of the present description; Tween 20 w / v 0.04%; L-histidine 20 mM; and 250 mM sucrose; and has a pH of 5.5. By way of another example, a parenteral formulation of the present comprises a lyophilized formulation comprising: 1) 15 mg / mL of an antibody of the subject; Tween 20 w / v 0.04%; L-histidine 20 mM; and 250 mM sucrose; and having a pH of 5.5; or 2) 75 mg / mL of an antibody of the present; Tween 20 w / v 0.04%; L-histidine 20 mM; and 250 mM sucrose; and having a pH of 5.5; or 3) 75 mg / mL of an antibody of the present; Tween 20 w / v 0.02%; L-histidine 20 mM; and 250 mM sucrose; and having a pH of 5.5; or 4) 75 mg / mL of an antibody of the present; Tween 20 w / v at 0.04%; L-histidine at 20 mM; and trehalose 250 mM; and has a pH of 5.5; or 5) 75 mg / mL of an antibody of the present; Tween 20 w / v at 0.02%; L-histidine 20 mM; and trehalose 250 mM; and has a pH of 5.5. By way of another example, a parenteral formulation of the present product is a liquid formulation comprising: 1) 7.5 mg / mL of an antibody of the present product; 0.02% Tween 20 w / v; 120 mM L-histidine; and 125 mM sucrose; and having a pH of 5.5; or 2) 37.5 mg / mL of an antibody of the present product; 0.02% Tween 20 w / v; 10 mM L-histidine; and 125 mM sucrose; and having a pH of 5.5; or 3) 37.5 mg / mL of an antibody of the present product; 0.01% Tween 20 w / v; 10 mM L-histidine; and 125 mM sucrose; and having a pH of 5.5; or 4) 37.5 mg / mL of an antibody of the present; Tween 20 w / v at 0.02%; L-histidine 10 mM; trehalose 125 mM; and has a pH of 5.5; or 5) 37.5 mg / mL of an antibody of the present; Tween 20 w / v at 0.01%; L-histidine 10 mM; and trehalose 125 mM; and has a pH of 5.5; or 6) 5 mg / mL of an antibody of the present; Tween 20 w / v at 0.02%; L-histidine 20 mM; and trehalose 250 mM; and has a pH of 5.5; or 7) 75 mg / mL of an antibody of the present; Tween 20 w / v at 0.0.02%; L-histidine 20 mM; and mannitol 250 mM; and has a pH of 5.5; or 8) 75 mg / mL of an antibody of the present; Tween 20 w / v 0.02%; L-histidine 20 mM; and sodium chloride 140 mM; and has a pH of 5.5; or 9) 150 mg / mL of an antibody of the present; Tween 20 w / v 0.02%; L-histidine 20 mM; and trehalose 250 mM; and has a pH of 5.5; or 10) 150 mg / mL of an antibody of the present; Tween 20 w / v 0.02%; L-histidine 20 mM; and mannitol 250 mM; and has a pH of 5.5; or 11) 150 mg / mL of an antibody of the present; Tween 20 w / v at 0.02%; L-histidine 20 mM; and sodium chloride 140 mM; and has a pH of 5.5; or 12) 10 mg / mL of an antibody of the present; Tween 20 w / v at 0.01%; L-histidine 20 mM; and sodium chloride 40 mM; and has a pH of 5.5. An antibody of the present product may be used in an aerosol formulation for administration by inhalation. The antibody of the present product may be formulated in acceptable pressurized propellants, such as dichlorodifluoromethane, propane, nitrogen, and the like. Aerosol formulations, such as nasal spray formulations, include purified aqueous or other solutions of the active agent with preservatives and isotonic agents. Such formulations are adjusted to a pH and isotonic state compatible with the nasal mucous membranes. Unit-dose forms for oral administration, such as syrups, elixirs, and suspensions, may be provided so that each unit dose, for example, a teaspoonful, tablespoonful, or tablet, contains a predetermined amount of the composition. Similarly, unit-dose forms for injection or intravenous administration may comprise an antibody present in a composition such as a solution in sterile water, normal saline, or another pharmaceutically acceptable carrier. The term unit dosage form, as used herein, refers to physically differentiated units suitable as unit dosages for human and animal subjects, wherein each unit contains a predetermined quantity of a humanized anti-Cls antibody of the hereof calculated as a quantity sufficient to produce the desired effect in association with a pharmaceutical diluent, carrier, or vehicle UO3 acceptable. The specifications for an antibody herein may depend on the particular antibody employed and the effect intended to be achieved, and the pharmacodynamics associated with each antibody in the host. Other modes of administration may also be used with a method described herein. For example, an antibody described herein may be formulated as suppositories and, in some cases, as aerosol and intranasal compositions. For suppositories, the vehicle composition will include traditional binders and carriers such as polyalkylene glycols or triglycerides. Such suppositories may be formed from mixtures containing the active ingredient in the range of approximately 0.5% to approximately 10% (w / w), for example, approximately 1% to approximately 2%. Intranasal formulations generally include vehicles that neither irritate the nasal mucosa nor significantly impair ciliary function. Diluents such as water, aqueous saline, or other known substances may be used. Nasal formulations may also contain preservatives such as, but not limited to, chlorobutanol and benzalkonium chloride. A surfactant may be present to enhance the absorption of the antibody by the nasal mucosa. An antibody of this type can be administered as an injectable formulation. Typically, injectable compositions are prepared as liquid solutions or suspensions; solid forms suitable for solution or suspension in liquid vehicles prior to injection can also be prepared. The preparation can also be emulsified, or the antibody can be encapsulated in liposomal vehicles. Suitable excipient vehicles include, for example, water, saline solution, dextrose, glycerol, ethanol, or similar substances, and combinations thereof. In addition, if desired, the vehicle may contain minor amounts of excipients such as wetting or emulsifying agents, or pH buffers. The actual methods for preparing the dosage forms are known to, or will be obvious to, those skilled in the art. See, for example, Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pennsylvania, 17th edition, 1985. The composition or formulation to be administered shall, in any case, contain an amount of an antibody suitable to achieve the desired state in the subject under treatment. Pharmaceutically acceptable excipients, such as vehicles, adjuvants, carriers, or diluents, are readily available to the public. In addition, pharmaceutically acceptable auxiliary substances, such as buffering or pH-adjusting agents, stabilizers, and similar wetting agents, are available. ML / a / ZUZZ / UU I UO3 are readily available to the public. In some embodiments, a humanized anti-Cls antibody of the present description is formulated in a controlled-release formulation. Sustained-release preparations can be prepared using methods known in the art. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, wherein the matrices are in the form of molded elements, for example, films or microcapsules. Examples of sustained-release matrices include polyesters, L-glutamic acid-ethyl-L-glutamate copolymers, non-degradable ethylene vinyl acetate, hydrogels, polylactides, lactic acid-glycolic acid copolymers, and poly-D-(-)-3-hydroxybutyric acid.The potential loss of biological activity and possible changes in immunogenicity of antibodies contained in sustained-release preparations can be prevented by the use of appropriate additives, control of moisture content, and the development of specific polymer matrix compositions. Controlled release within the scope of this description may be interpreted to mean any number of extended-release dosage forms. The following terms may be considered substantially equivalent to controlled release for the purposes of this description: continuous release, controlled release, delayed release, depot, extended release, gradual release, immediate release, long-term release, scheduled release, prolonged release, proportionate release, elongated release, repository, delay, slow release, spaced release, sustained release, planned coating, gradual release, delayed action, extended action, time-stratified action, extended duration, prolonged action, repeated action, slowing effect, sustained action, and sustained-action drugs.Further discussions of these terms can be found in Lesczek Krowczynski, Extended-Release Dosage Forms, 1987 (CRC Press, Inc.). The various controlled-release technologies cover a very broad spectrum of drug dosage forms. Controlled-release technologies include, but are not limited to, physical and chemical systems. Physical systems include, but are not limited to, reservoir systems with rate-controlling membranes, such as microencapsulation, macroencapsulation, and membrane systems; reservoir systems without rate-controlling membranes, such as hollow fibers, ultra-microporous cellulose triacetate, and porous polymeric foams and substrates; monolithic systems, which include those systems physically dissolved in non-porous, polymeric, or elastomeric matrices (e.g., non-erodible, erodible, environmental ingress, and degradable), and materials physically dispersed in non-porous, polymeric, or elastomeric matrices (e.g., non-erodible, erodible, environmental ingress, and degradable); laminated structures, which include reservoir layers chemically similar to or different from the external control layers; and other physical methods, such as osmotic pumps, or adsorption onto ion-exchange resins. Chemical systems include, but are not limited to, chemical erosion of polymer matrices (e.g., heterogeneous or homogeneous erosion) or biological erosion of a polymer matrix (e.g., heterogeneous or homogeneous). A further analysis of system categories for controlled release can be found in Agis F. Kydonieus, Controlled Release Technologies: Methods, Theory and Applications, 1980 (CRC Press, Inc.). A number of controlled-release drug formulations are being developed for oral administration. These include, but are not limited to, osmotic pressure-controlled gastrointestinal delivery systems; hydrodynamic pressure-controlled gastrointestinal delivery systems; Gastrointestinal delivery systems include membrane-permeable controlled-release devices, such as microporous membrane-permeable controlled-release devices; gastric fluid-resistant controlled-release devices; gel-diffusion controlled-release systems; and ion-exchange controlled-release systems, including cationic and anionic drugs. Additional information regarding controlled-release drug delivery systems can be found in Yie W. Chien, *Novel Drug Delivery Systems*, 1992 (Marcel Dekker, Inc.). Dosages An attending physician or other qualified medical personnel can determine an appropriate dosage based on several clinical factors. As is known in medical practice, dosages for any patient depend on many factors, including the patient's size, body surface area, age, the specific compound being administered, the patient's sex, the timing and route of administration, general health, and other drugs being administered concurrently. An antibody of the type present can be administered in amounts between 1 ng / kg of body weight and 20 mg / kg of body weight per dose, for example, between 0.1 mg / kg of body weight and 10 mg / kg of body weight, or between 0.5 mg / kg of body weight and 5 mg / kg of body weight; however, doses below or above this example range are anticipated, especially when considering the factors mentioned above.If the regimen is a continuous infusion, it may also be in the range of 1 pg to 10 mg per kilogram of body weight per minute. In some formulations, a dose of a humanized anti-Cls antibody of the present description is in the range of 0.001 pg to 1000 pg; however, dosages below or above this example range are anticipated, especially considering the factors mentioned above. In some formulations, the dosage may vary, for example, from approximately 0.0001 to 100 mg / kg, or from approximately 0.01 to 5 mg / kg (e.g., 0.02 mg / kg, 0.25 mg / kg, 0.5 mg / kg, 0.75 mg / kg, 1 mg / kg, 2 mg / kg, etc.) of body weight. For example, dosages may be 1 mg / kg of body weight or 10 mg / kg of body weight, or within the range of 1–10 mg / kg, or at least 1 mg / kg. It is intended that the doses within the aforementioned ranges are also within the range of the invention. In some formulations, a humanized anti-Cls antibody of the present description is administered in an amount that provides a peak serum concentration of from about 1 pg / ml to about 1 mg / ml, for example, from about 1 pg / ml to about 2.5 pg / ml, from about 2.5 pg / ml to about 5 pg / ml, from about 5 pg / ml to about 7.5 pg / ml, from about 7.5 pg / ml to about 10 pg / ml, from about 10 pg / ml to about 25 pg / ml, from about 25 pg / ml to about 50 pg / ml, from about 50 pg / ml to about 100 pg / ml, from about 100 pg / ml to about 250 pg / ml, from about 250 pg / ml to about 500 pg / ml, from around 500 pg / ml to around 750 pg / ml, or from around 750 pg / ml to around 1000 pg / ml.In some modalities, a subject anti-Cls antibody is administered in an amount that provides a peak serum concentration greater than 1 mg / ml, for example, from about 1 mg / ml to about 2 mg / ml, from about 2 mg / ml to about 5 mg / ml, or from about 5 mg / ml to about 10 mg / ml. A humanized antibody of the present description can be administered according to any schedule and for any period of time. Experts will quickly observe that dosage levels and administration schedules can vary depending on the specific antibody, the severity of symptoms, and the subject's susceptibility to side effects. Those skilled in the technique can determine preferred dosages and administration schedules for a given compound using a variety of methods. Routes of administration An antibody of the present is administered to an individual using any method and route available suitable for drug delivery, including in vivo and ex vivo methods, as well as systemic and localized routes of administration. Conventional and pharmaceutically acceptable routes of administration include intranasal, intramuscular, intratracheal, intrathecal, intracranial, subcutaneous, intradermal, topical, intravenous, intraperitoneal, intra-arterial (e.g., via the carotid artery), spinal or brain administration, rectal, nasal, oral, and other enteral and parenteral routes. Routes of administration may be combined, if desired, or adjusted according to the antibody and / or the desired effect. The antibody composition hereof may be administered as a single dose or in multiple doses. In some formulations, an antibody composition hereof is administered orally. In some formulations, an antibody composition hereof is administered by inhalation. In some formulations, an antibody composition hereof is administered intranasally.In some modalities, an antibody composition of the present is administered locally. In some modalities, an antibody composition of the present is administered intracranially. In some modalities, an antibody composition of the present is administered intravenously. In some modalities, an antibody composition of the present is administered subcutaneously. In some modalities, an antibody composition of the present is administered intramuscularly. In some modalities, an antibody composition of the present is administered intrathecally. An antibody of the present description can be administered to a host using any conventional method and route suitable for the administration of conventional drugs, including systemic and local routes. In general, the routes of administration contemplated by the invention include, but are not necessarily limited to, enteral, parenteral, or inhalation routes. Parenteral routes of administration other than inhalation include, but are not necessarily limited to, topical, transdermal, subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intrathecal, and intravenous routes—that is, any route of administration other than through the alimentary canal. Parenteral administration may be performed to effect systemic or local delivery of an antibody. When systemic delivery is desired, administration typically involves mucosal or topical administration of pharmaceutical preparations that are systemically or invasively absorbed. An antibody present in this form can also be administered to the subject via enteral administration. Enteral routes of administration include, but are not necessarily limited to, oral or rectal administration (e.g., using a suppository). Treatment is understood to mean at least an improvement in the symptoms associated with the pathological condition affecting the host, where improvement is used in a broad sense to refer to at least a reduction in the magnitude of a parameter, e.g., symptom, associated with the pathological condition being treated, such as a complement-mediated disorder or disease. As such, treatment also includes situations where the pathological condition, or at least the symptoms associated with it, are completely inhibited (e.g., prevented from occurring) or stopped (e.g., terminated), so that the host no longer suffers from the pathological condition, or at least from the symptoms that characterize it. In some delivery systems, a humanized anti-Cls antibody of the present description is administered by injection and / or oral administration, for example, into a site in a cerebral artery or directly into brain tissue. A humanized antibody of the present description can also be delivered directly to a target site, for example, by biologic delivery to the target site. A variety of hosts (where the term host is used interchangeably herein with the terms subject, individual, and patient) may be treated according to the methods herein. Generally, such hosts are mammals, where the terms are generally used to describe organisms within the class Mammalia, including the order Carnivora (e.g., cats), Herbivora (e.g., cattle, horses, and sheep), Omnivora (e.g., dogs, goats, and pigs), Rodentia (e.g., mice, guinea pigs, and rats), and Primates (e.g., humans, chimpanzees, and monkeys). In some modalities, the host is an individual that possesses a complement system, such as a mammal, fish, or invertebrate.In some forms, the host is a mammal, fish, or invertebrate pet, farm animal, working animal, zoo animal, or laboratory animal that possesses the complement system. In some forms, the host is human. The embodiments include compositions comprising a suitable container for holding a composition comprising an anti-Cls antibody of the present for administration to an individual. For example, a subject antibody may be disposed within a suitable container for holding a pharmaceutical composition. The container may be, for example, a bottle (e.g., with a closure device, such as a cap), a blister pack (e.g., capable of sealing one or more doses per pack), a vial, flexible packaging (e.g., sealed Mylar or plastic bags), an ampoule (for unit doses in solution), a dropper, a syringe, thin film, a tube, and the like. In some embodiments, a container, such as a sterile container, comprises a pharmaceutical composition of the present. In some embodiments, the container is a bottle or a syringe. In some embodiments, the container is a bottle.In some versions, the container is a syringe. Unit-dose kits of an anti-Cls antibody of the description described herein are provided, for example, in oral or injectable doses. These kits will include, in addition to the containers holding the unit doses, an informational package insert describing the inherent benefits of using the antibody in treating the pathological condition of interest. The preferred compounds and unit doses are those described above. Methods for treating a complement-mediated disease or disorder This description provides methods for treating a complement-mediated disease or disorder. The methods generally involve administering an effective amount of a humanized anti-Cls antibody of this description, or a pharmaceutical composition comprising such an antibody, to an individual in need. In some cases, administration of an anti-Cls antibody of this description modulates complement Cls activity in a cell, tissue, fluid, or organ of an individual and treats the complement-mediated disease or disorder. This description also provides methods for inhibiting the activation of complement component C4 in an individual, the methods comprising administering to the individual an effective amount of a humanized anti-Cls antibody of this description or a pharmaceutical composition comprising such an antibody.This description provides methods for inhibiting complement Cls activity in an individual, the methods comprising administering to the individual an effective amount of a humanized anti-Cls antibody of this description or a pharmaceutical composition comprising such an antibody. This description also provides methods for reducing the level of a complement component cleavage product in an individual (e.g., in a fluid, tissue, or organ in an individual), the methods comprising administering to the individual an effective amount of a humanized anti-Cls antibody of this description or a pharmaceutical composition comprising such an antibody. In some cases, a method described herein for treating an individual with a complement-mediated disorder or disease comprises administering to the individual an effective quantity of a humanized anti-Cls antibody described herein or an effective quantity of a pharmaceutical composition comprising: a) a humanized anti-Cls antibody described herein; and a pharmaceutically acceptable excipient suitable for administration to such an individual. In some embodiments, the individual is a mammal. In some embodiments, the individual is a human being. Administration may be by any route known to those skilled in the art, including those described herein. In some embodiments, administration is intravenous. In some embodiments, administration is intrathecal. In some embodiments, administration is subcutaneous. In some embodiments, administration is intramuscular. In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition hereunder comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces the level of a complement component cleavage product in the individual (e.g., in a fluid, tissue, or organ in the individual).In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition hereunder comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces the level of a complement component cleavage product in the individual (e.g., in a fluid, tissue, or organ in the individual) by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%, compared to the level of the complement component cleavage product in the absence of treatment with the humanized anti-Cls antibody, e.g., prior to treatment with the humanized anti-Cls antibody. In some embodiments, the individual is a mammal.In some forms, the individual is a human being. Administration may be by any route known to those skilled in the art, including those described herein. In some forms, administration is intravenous. In some forms, the route of administration is intrathecal. In some forms, the route of administration is intravenous. In some forms, the route of administration is subcutaneous. In some forms, the route of administration is intramuscular. In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition herein comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces the activity of the classical complement pathway in the individual (e.g., in a fluid, tissue, or organ in the individual). In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition herein comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces, within approximately 48 hours, within approximately 24 hours, within approximately 12 hours, within approximately 8 hours,or within approximately 4 hours of administration of the humanized anti-Cls antibody, the activity of the classical complement pathway in the individual (e.g., in a fluid, tissue, or organ in the individual) is at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%, compared to the activity of the classical complement pathway in the fluid, tissue, or organ in the absence of treatment with the humanized anti-Cls antibody, e.g., before treatment with the humanized anti-Cls antibody. In some modalities, the individual is a mammal. In some modalities, the individual is a human. Administration of the humanized anti-Cls antibody may be by any route known to those skilled in the art, including those described herein. In some modalities,The route of administration is intrathecal. In some modalities, the route of administration is intravenous. In some modalities, the route of administration is subcutaneous. In some modalities, the route of administration is intramuscular. The level of activity of the classical complement pathway can be determined using any of a variety of methods. By way of non-exhaustive example, the activity of the classical complement pathway can be determined ex vivo, for example, by determining the level of activity of the classical complement pathway in a blood, serum, or plasma sample obtained from the individual. For example, the classical complement pathway in the blood, serum, or plasma sample can be activated ex vivo, and the amount of a complement component cleavage product (such as C5b-9) generated by such activation can be determined. In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition herein comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces the activity of the classical complement pathway in the individual (e.g., in a fluid, tissue, or organ in the individual). In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition herein comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces, within approximately 48 hours, within approximately 24 hours, within approximately 12 hours, within approximately 8 hours,or within approximately 4 hours of administration of the humanized anti-Cls antibody, the level of classical complement pathway activity in the individual (e.g., in a fluid, tissue, or organ in the individual) is at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%, compared to the level of classical complement pathway activity in the fluid, tissue, or organ in the absence of treatment with the humanized anti-Cls antibody, e.g., before treatment with the humanized anti-Cls antibody. In some modalities, the individual is a mammal. In some modalities, the individual is a human. Administration of the humanized anti-Cls antibody may be by any route known to those skilled in the art, including those described herein. In some modalities, the route of administration is intrathecal. In some modalities,The route of administration is intravenous. In some forms, the route of administration is subcutaneous. In some forms, the route of administration is intramuscular. In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition herein comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces the activity of the classical complement pathway in the individual (e.g., in a fluid, tissue, or organ in the individual). In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition herein comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, maintains a reduction in the level of activity of the classical complement pathway in the individual (e.g., in a fluid, tissue, or organ in the individual) of at least 10%.at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%, compared to the level of classical complement pathway activity in the fluid, tissue, or organ in the absence of treatment with the humanized anti-Cls antibody, for example, before treatment with the humanized anti-Cls antibody, where the reduction is maintained for a period of time from about 4 hours to about 30 days (for example, from 4 hours to 8 hours, from 8 hours to 24 hours, from 2 days to 4 days, from 4 days to 7 days, from 7 days to 14 days, from 14 days to 21 days, or from 21 days to 30 days). In some modalities, the individual is a mammal. In some forms, the individual is a being, Human UO3. The humanized anti-Cls antibody can be administered via any route known to those skilled in the art, including those described herein. In some modalities, the route of administration is intrathecal. In some modalities, the route of administration is intravenous. In some modalities, the route of administration is subcutaneous. In some modalities, the route of administration is intramuscular. In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition herein comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces the activity of the classical complement pathway in the individual (e.g., in a fluid, tissue, or organ in the individual). In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition herein comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, maintains a reduction in the level of activity of the classical complement pathway in the individual (e.g., in a fluid, tissue, or organ in the individual) of at least 50%.UO3 less than 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%, compared to the level of classical complement pathway activity in the fluid, tissue, or organ in the absence of treatment with the humanized anti-Cls antibody, for example, before treatment with the humanized anti-Cls antibody, where the reduction is maintained for a period of time from about 4 hours to about 21 days (for example, from 4 hours to 8 hours, from 8 hours to 24 hours, from 2 days to 4 days, from 4 days to 7 days, from 7 days to 14 days, or from 14 days to 21 days). In some modalities, the individual is a mammal. In some modalities, the individual is a human. The humanized anti-Cls antibody can be administered via any route known to practitioners, including those described herein. In some cases, the route of administration is intrathecal.In some forms, the route of administration is intravenous. In some forms, the route of administration is subcutaneous. In some forms, the route of administration is intramuscular. In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition hereof comprising a humanized anti-Cls antibody of UO3, as described herein, is an amount that, when administered in one or more doses to an individual in need, reduces the level of a complement component cleavage product in the individual (e.g., in a fluid, tissue, or organ in the individual). In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition herein comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces, within approximately 48 hours, within approximately 24 hours, within approximately 12 hours, within approximately 8 hours, or within approximately 4 hours of administration of the humanized anti-Cls antibody, the level of a complement component cleavage product (e.g., in a fluid, tissue, or organ in the individual) by at least 10%, at least 20%,at least 30%, at least 40%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%, compared to the level of complement component cleavage product in the fluid, tissue, or organ in the absence of treatment with the humanized anti-Cls antibody, for example, before treatment with the humanized anti-Cls antibody. In some modalities, the individual is a mammal. In some modalities, the individual is a human. Administration of the humanized anti-Cls antibody may be by any route known to those skilled in the art, including those described herein. In some modalities, the route of administration is intrathecal. In some modalities, the route of administration is intravenous. In some modalities, the route of administration is subcutaneous. In some modalities, the route of administration is intramuscular. In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition herein comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces the level of a complement component cleavage product in the individual (e.g., in a fluid, tissue, or organ in the individual). In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition herein comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces, within approximately 48 hours, within approximately 24 hours, within IVIA / a / ZUZZ / UU I UO3 within approximately 12 hours, within approximately 8 hours, or within approximately 4 hours of administration of the humanized anti-Cls antibody, the level of a complement component cleavage product in the individual (e.g., in a fluid, tissue, or organ in the individual) is at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%, compared to the level of the complement component cleavage product in the fluid, tissue, or organ in the absence of treatment with the humanized anti-Cls antibody, e.g., before treatment with the humanized anti-Cls antibody. In some modalities, the individual is a mammal. In some modalities, the individual is a human. The administration of the humanized anti-Cls antibody can be by any route known to experts in the technique, including those described herein.In some forms, the route of administration is intrathecal. In some forms, the route of administration is intravenous. In some forms, the route of administration is subcutaneous. In some forms, the route of administration is intramuscular. In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition of the An effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition hereof comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces the level of a complement component cleavage product in the individual (e.g., in a fluid, tissue, or organ in the individual). In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition hereof comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, maintains a reduction in the level of a complement component cleavage product in the individual (e.g., in a fluid, tissue, or organ in the individual) of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, or at least 80%.at least 85%, at least 90%, at least 95% or 100%, compared to the complement component cleavage product level in the fluid, tissue or organ in the absence of treatment with the humanized anti-Cls antibody, e.g., before treatment with the humanized anti-Cls antibody, wherein the reduction is maintained for a period of time from about 4 hours to about 30 days (e.g., from 4 hours to 8, UO3 hours, 8 hours to 24 hours, 2 days to 4 days, 4 days to 7 days, 7 days to 14 days, 14 days to 21 days, or 21 days to 30 days). In some modalities, the individual is a mammal. In some modalities, the individual is a human. Administration of the humanized anti-Cls antibody may be by any route known to those skilled in the art, including those described herein. In some modalities, the route of administration is intrathecal. In some modalities, the route of administration is intravenous. In some modalities, the route of administration is subcutaneous. In some modalities, the route of administration is intramuscular. In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition herein comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces the level of a complement component cleavage product in the individual (e.g., in a fluid, tissue, or organ in the individual). In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition herein comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, maintains a reduction in the level of a complement component cleavage product in the individual (e.g., in a fluid, tissue, or organ in the individual).tissue or organ in the individual) of at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%, compared to the complement component cleavage product level in the fluid, tissue, or organ in the absence of treatment with the humanized anti-Cls antibody, for example, before treatment with the humanized anti-Cls antibody, where the reduction is maintained for a period of time from about 4 hours to about 21 days (for example, from 4 hours to 8 hours, from 8 hours to 24 hours, from 2 days to 4 days, from 4 days to 7 days, from 7 days to 14 days, or from 14 days to 21 days). In some modalities, the individual is a mammal. In some modalities, the individual is a human. The humanized anti-Cls antibody can be administered via any route known to practitioners, including those described herein. In some modalities,The route of administration is intrathecal. In some forms, the route of administration is intravenous. In some forms, the route of administration is subcutaneous. In some forms, UO3 the route of administration is intramuscular. In some cases, an effective amount of a humanized anti-Cls antibody of the present description, or an effective amount of a pharmaceutical composition hereunder comprising a humanized anti-Cls antibody of the present description, is an amount that, when administered in one or more doses to an individual in need, reduces the production of C4b2a (i.e., complement C4b and C2a complex; also known as C3 convertase) in the individual (or in a fluid, tissue, or organ of the individual) by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%, compared to the amount of C4b2a produced in the individual, or the fluid, tissue, or organ, in the absence of treatment with the humanized anti-Cls antibody, for example, prior to treatment with the humanized anti-Cls antibody.In some forms, the individual is a mammal. In some forms, the individual is a human being. Administration may be by any route known to those skilled in the art, including those described herein. In some forms, administration is intravenous. In some forms, the route of administration is intrathecal. In some forms, the route of administration is intravenous. In some forms, the route of administration. ML / a / ZUZZ / UU I UO3 is subcutaneous. In some forms, the route of administration is intramuscular. This description provides a method for modulating complement activation. In some embodiments, the method inhibits complement activation, for example, by reducing C4b2a production. In some embodiments, this description provides a method for modulating complement activation in an individual with a complement-mediated disorder or disease, wherein the method comprises administering to the individual a humanized anti-Cls antibody of this description or a pharmaceutical composition of this description, wherein the pharmaceutical composition comprises a humanized anti-Cls antibody of this description. In some embodiments, such a method inhibits complement activation. In some embodiments, the individual is a mammal. In some embodiments, the individual is a human. Administration may be by any route known to those skilled in the art, including those described herein.In some forms, administration is intravenous. In some forms, administration is intrathecal. In some forms, administration is subcutaneous. In some forms, the route of administration is intramuscular. A complement-mediated disorder or disease is a disorder characterized by an abnormal amount of complement cells or an abnormal level of proteolytic activity of complement cells in a cell, tissue, fluid, or organ of an individual. In some cases, a complement-mediated disorder or disease is characterized by the presence in a cell, tissue, or fluid of an elevated (higher than normal) amount of complement (Cls) or an elevated level of complement (Cls) activity. For example, in some cases, a complement-mediated disorder or disease is characterized by the presence in brain tissue and / or cerebrospinal fluid of an elevated amount and / or elevated activity of complement (Cls). An elevated-than-normal amount of complement (Cls) in a cell, tissue, or fluid indicates that the amount of complement in the cell, tissue, or fluid is greater than a normal control level—for example, higher than a normal control level for an individual or a population of individuals of the same age group.A higher than normal level of complement-mediated cleavage (Cls) activity in a cell, tissue, organ, or fluid indicates that the proteolytic cleavage performed by Cls in that cell, tissue, organ, or fluid is greater than a normal control level—for example, higher than a normal control level for an individual or a population of individuals of the same age group. In some cases, this may be the case for an individual with a complement-mediated disorder or disease. 100 exhibits one or more additional symptoms of such disorder or disease. In other cases, a complement-mediated disorder or disease is characterized by the presence in a cell, tissue, or fluid of a lower-than-normal amount of complement (Cls) or a lower level of complement activity. For example, in some cases, a complement-mediated disorder or disease is characterized by the presence in brain tissue and / or cerebrospinal fluid of a lower amount and / or lower activity of complement (Cls). A lower-than-normal amount of complement (Cls) in a cell, tissue, or fluid indicates that the amount of complement in the cell, tissue, or fluid is less than a normal control level—for example, lower than a normal control level for an individual or a population of individuals of the same age group.A lower-than-normal level of complement-mediated cleavage (Cls) activity in a cell, tissue, or fluid indicates that the proteolytic cleavage performed by Cls in the cell, tissue, or fluid is less than a normal control level—for example, lower than a normal control level for an individual or a population of individuals of the same age group. In some cases, an individual with a complement-mediated disorder or disease exhibits one or more additional symptoms of that disorder or disease. A complement-mediated disorder or disease is a 101. A disorder or disease in which the quantity or activity of complement receptors is such as to cause the disease or disorder in an individual. In some categories, the complement-mediated disorder or disease is selected from the group consisting of alloimmune disease, autoimmune disease, cancer, hematologic disease, infectious disease, inflammatory disease, ischemia-reperfusion injury, neurodegenerative disease, neurodegenerative disorder, eye disease, kidney disease, transplant rejection, vascular disease, and vasculitis. In some categories, the complement-mediated disease or disorder is an autoimmune disease. In some categories, the complement-mediated disease or disorder is an alloimmune disease. In some categories, the complement-mediated disease or disorder is cancer.In some forms, complement-mediated disease or disorder is an infectious disease. In some forms, complement-mediated disease or disorder is an inflammatory disease. In some forms, complement-mediated disease or disorder is a hematologic disease. In some forms, complement-mediated disease or disorder is ischemia-reperfusion injury. In some forms, complement-mediated disease or disorder is an ocular disease. In some forms... IVIA / a / ZUZZ / UU I UO3 102 Complement-mediated disease or disorder is a kidney disease. In some forms, complement-mediated disease or disorder is transplant rejection. In some forms, complement-mediated disease or disorder is antibody-mediated transplant rejection. In some forms, complement-mediated disease or disorder is a vascular disease. In some forms, complement-mediated disease or disorder is a vasculitis disorder. In some forms, complement-mediated disease or disorder is a neurodegenerative disease or disorder. In some forms, complement-mediated disease is a neurodegenerative disease. In some forms, complement-mediated disorder is a neurodegenerative disorder. Examples of complement-mediated disorders or diseases include, but are not limited to, age-related macular degeneration, Alzheimer's disease, amyotrophic lateral sclerosis, anaphylaxis, argyrophilic granulophilic disease, arthritis (e.g., rheumatoid arthritis), asthma, atherosclerosis, atypical hemolytic uremic syndrome, autoimmune diseases (including, for example, autoimmune hemolytic anemia (AIHA); mild AIHA; mixed AIHA; etc.), Barraquer-Simons syndrome, Behget's disease, 103 British-type amyloid angiopathy, spindle pemphigoid, Buerger's disease, Clq nephropathy, cancer, catastrophic antiphospholipid syndrome, cerebral amyloid angiopathy, cold agglutinin disease, corticobasal degeneration, Creutzfeldt-Jakob disease, Crohn's disease, cryoglobulinemic vasculitis, dementia pugilistica, dementia with Lewy bodies (DLB), diffuse neurofibrillary tangles with calcifications, discoid lupus erythematosus, Down syndrome, Evan syndrome, focal segmental glomerulosclerosis, formal thinking disorder, frontotemporal dementia (FTD), frontotemporal dementia with parkinsonism associated with chromosome 17, frontotemporal lobar degeneration, Gerstmann-Straussler-Scheinker disease, Guillain-Barré syndrome, disease of Hallervorden-Spatz, hemolytic-uremic syndrome, hereditary angioedema, hypophosphastasis, idiopathic pneumonia syndrome, immune complex diseasesinclusion body myositis, infectious disease (e.g., disease caused by bacterial agents (e.g., Neisseria meningitidis or Streptococcus), viral agents (e.g., human immunodeficiency virus (HIV)), or other infectious agents), inflammatory disease, ischemia / reperfusion injury, mild cognitive impairment, immune thrombocytopenic purpura (ITP, UO3 104 English), molybdenum cofactor deficiency (MoCD) type A, membranoproliferative glomerulonephritis (MPGN) I, membranoproliferative glomerulonephritis (MPGN) II (dense deposit disease), membranous nephritis, multi-infarct dementia, lupus (e.g., systemic lupus erythematosus (SLE)), glomerulonephritis, Kawasaki disease, multifocal motor neuropathy, multiple sclerosis, multiple system atrophy, myasthenia gravis, myocardial infarction, myotonic dystrophy, neuromyelitis optica, Niemann-Pick disease type C, non-Guamannian motor neuron disease with neurofibrillary tangles, Parkinson's disease, Parkinson's disease with dementia, paroxysmal nocturnal hemoglobinuria, pemphigus vulgaris, Pick's disease, parkinsonism post-encephalitic syndrome, polymyositis, cerebral amyloid angiopathy due to prion protein, progressive subcortical gliosis,progressive supranuclear palsy, psoriasis, sepsis, Shiga toxin-producing E. coli (STEC)-HuS, spinal muscular atrophy, stroke, subacute sclerosing panencephalitis, tangle-only dementia, transplant rejection, vasculitis (e.g., ANCA-associated vasculitis), Wegner's granulomatosis, sickle cell disease, cryoglobulinemia, mixed cryoglobulinemia, essential mixed cryoglobulinemia, type II mixed cryoglobulinemia 105 mixed cryoglobulinemia type III, nephritis, drug-induced thrombocytopenia, lupus nephritis, acquired epidermolysis bullosa, delayed hemolytic reaction to a transfusion, hypocomplementemic urticarial vasculitis syndrome, pseudophakic horny keratopathy, and platelet refractoriness. In some forms, complement-mediated disease or disorder includes Alzheimer's disease. In some forms, complement-mediated disease or disorder includes Parkinson's disease. In some forms, complement-mediated disease or disorder includes transplant rejection. In some forms, complement-mediated disease or disorder is antibody-mediated transplant rejection. In some embodiments, a humanized anti-Cls antibody of the present description prevents or delays the onset of at least one symptom of a complement-mediated disease or disorder in an individual. In some embodiments, an anti-Cls antibody of the present description reduces or eliminates at least one symptom of a complement-mediated disease or disorder in an individual. Examples of symptoms include, but are not limited to, symptoms associated with autoimmune diseases, cancer, hematologic disease, infectious disease, inflammatory disease, and ischemic injury. 106 reperfusion, neurodegenerative disease, neurodegenerative disorder, kidney disease, transplant rejection, eye disease, vascular disease, or a vasculitis disorder. The symptom may be a neurological symptom, for example, impaired cognitive function, memory impairment, loss of motor function, etc. The symptom may also be the activity of Cls protein in a cell, tissue, or fluid of an individual. The symptom may also be the extent of complement activation in a cell, tissue, or fluid of an individual. In some embodiments, administering a humanized anti-Cls antibody of the present description to an individual modulates complement activation in a cell, tissue, or fluid of that individual. In some embodiments, administering an anti-Cls antibody of the present description to an individual inhibits complement activation in a cell, tissue, or fluid of that individual. For example, in some embodiments, a humanized anti-Cls antibody of the present description, when administered in one or more doses as monotherapy or in combination therapy to an individual having a complement-mediated disease or disorder, inhibits complement activation in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least 107 around 50%, at least around 60%, at least around 70%, at least around 80%, at least around 90%, or more than 90%, compared to complement activation in the individual prior to treatment with the anti-Cls antibody. In some embodiments, a humanized anti-Cls antibody of the present description reduces C3 deposition on red blood cells (for example, in some embodiments, an anti-Cls antibody of the present description reduces the deposition of C3b, iC3b, etc., on RBCs). In some embodiments, an anti-Cls antibody of the present description inhibits complement-mediated red blood cell lysis. In some embodiments, a humanized anti-Cls antibody of the present description reduces the deposition of C3 in platelets; for example, in some embodiments, an anti-Cls antibody of the present description reduces the deposition of C3b, iC3b, etc., in platelets. In some modalities, administering a humanized anti-Cls antibody as described herein results in an outcome selected from the group consisting of: (a) a reduction in complement activation; (b) an improvement in cognitive function; (c) a reduction in neuronal loss; (d) a reduction in glial cell activation; (e) a reduction in lymphocyte infiltration; (f) a UO3 (g) a reduction in macrophage infiltration; (h) a reduction in antibody deposition; (i) a reduction in glial cell loss; (j) a reduction in oligodendrocyte loss; (k) a reduction in dendritic cell infiltration; (l) a reduction in neutrophil infiltration; (e) a reduction in red blood cell lysis; (m) a reduction in red blood cell phagocytosis; (n) a reduction in platelet phagocytosis; (o) a reduction in platelet lysis; (p) an improvement in transplanted graft survival; (q) a reduction in macrophage-mediated phagocytosis; (r) an improvement in vision; (s) an improvement in motor control; (t) an improvement in thrombus formation; (u) an improvement in coagulation; (v) an improvement in renal function; (w) a reduction in antibody-mediated complement activation; (x) a reduction in autoantibody-mediated complement activation; (y) an improvement in anemia; (aa) a reduction in demyelination;(ab) reduction of eosinophilia; (ac) a reduction in C3 deposition in red blood cells (e.g., a reduction in the deposition of C3b, iC3b, etc., in RBCs); and (ad) a reduction in C3 deposition in platelets (e.g., a reduction in the deposition of C3b, iC3b, etc., in platelets); and (ae) a reduction in the production of the anaphylatoxin; (af) a reduction in autoantibody-mediated blister formation; (ag) a reduction in pruritus-induced blistering; 109 autoantibody-mediated; (ah) a reduction in autoantibody-induced erythema; (ai) a reduction in autoantibody-mediated skin erosion; (aj) a reduction in red blood cell destruction due to transfusion reactions; (ak) a reduction in red blood cell lysis due to alloantibodies; (al) a reduction in hemolysis due to transfusion reactions; (am) a reduction in alloantibody-mediated platelet lysis; (an) a reduction in platelet lysis due to transfusion reactions; (ao) a reduction in mast cell activation; (ap) a reduction in histamine release from mast cells; (aq) a reduction in vascular permeability; (ar) a reduction in edema; (as) a reduction in complement deposition in the endothelium of the transplanted graft; (at) a reduction in anaphylatoxin generation in the endothelium of the transplanted graft; (au) a reduction in the separation of the dermo-epidermal junction;(av) a reduction in anaphylatoxin generation at the dermo-epidermal junction; (aw) a reduction in alloantibody-mediated complement activation in the endothelium of the transplanted graft; (ax) a reduction in antibody-mediated loss from the neuromuscular junction; (ay) a reduction in complement activation at the neuromuscular junction; (az) a reduction in anaphylatoxin generation at the neuromuscular junction; (ba) a reduction; 110 in complement deposition at the neuromuscular junction; (bb) a reduction in paralysis; (be) a reduction in numbness; (bd) increased bladder control; (be) increased bowel control; (bf) a reduction in autoantibody-associated mortality; and (bg) a reduction in autoantibody-associated morbidity. In some modalities, an anti-Cls antibody of the present, when administered in one or more doses as monotherapy or in combination therapy to an individual having a complement-mediated disease or disorder, can achieve a reduction of at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, of one or more of the following outcomes: (a) complement activation; (b) worsening of cognitive function; (c) neuronal loss; (d) glial cell activation; (e) lymphocyte infiltration; (f) macrophage infiltration; (g) antibody deposition; (h) glial cell loss; (i) oligodendrocyte loss; (j) dendritic cell infiltration; (k) neutrophil infiltration;(1) lysis of red blood cells; (m) phagocytosis of red blood cells; (n) phagocytosis of platelets; (o) lysis of platelets; (p) rejection; 111 of transplanted graft; (q) macrophage-mediated phagocytosis; (r) vision loss; (s) antibody-mediated complement activation; (t) autoantibody-mediated complement activation; (u) demyelination; (v) eosinophilia; compared to the level or degree of the outcome in the individual prior to treatment with the anti-Cls antibody. In some modalities, an anti-Cls antibody of the present, when administered in one or more doses as monotherapy or in combination therapy to an individual having a complement-mediated disease or disorder, can achieve an improvement of at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, in one or more of the following outcomes: a) cognitive function; b) transplanted graft survival; c) vision; d) motor control; e) thrombus formation; f) coagulation; g) renal function; and h) hematocrit (red blood cell count), compared to the level or degree of the outcome in the individual prior to treatment with the anti-Cls antibody. In some modalities, administering an anti-antibody UO3 112 Humanized Cls of the present description reduces complement activation in an individual. For example, in some modalities, an anti-Cls antibody of the present, when administered in one or more doses as monotherapy or in combination therapy to an individual having a complement-mediated disease or disorder, reduces complement activation in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to complement activation in the individual before treatment with the anti-Cls antibody. In some modalities, administering a humanized anti-Cls antibody as described herein improves cognitive function in the individual. For example, in some modalities, an anti-Cls antibody as described herein, when administered in one or more doses as monotherapy or in combination therapy to an individual with a complement-mediated disease or disorder, improves cognitive function in the individual by at least approximately 10%, at least approximately 15%, at least approximately 20%, at least approximately 25%, at least approximately 30%, at least 113 around 40%, at least around 50%, at least around 60%, at least around 70%, at least around 80%, at least around 90%, or more than 90%, compared to cognitive function in the individual IVIA / a / ZUZZ / UU I UO3 before treatment with the anti-Cls antibody. In some modalities, administering a humanized anti-Cls antibody as described herein reduces the rate of cognitive decline in the individual. For example, in some modalities, an anti-Cls antibody of the present description, when administered as monotherapy or in combination therapy, reduces the rate of cognitive decline in the individual by approximately [number of] doses. at least around 10 at least around 20 at least around 30 at least around 50 at least around 70 at least around or more than 90 compared to the rate of cognitive decline in the individual before treatment with the anti-Cls antibody. In some cases, administering a humanized anti-Cls antibody as described here to an individual reduces neuronal loss in that individual. For example, 114 In some modalities, an anti-Cls antibody of the present, when administered in one or more doses as monotherapy or in combination therapy to an individual having a complement-mediated disease or disorder, UO3 reduces the loss of neurons in the individual by at least around 10 O r at least around 15 θ L at least around 20 % r at least around 25 O. of at least around 30 or at least around 40 or at least around 50 0 r at least around 60 O r at least around 70 'qr at least around 80 oor at least around 90%, or more than 90%, compared to the loss of neurons in the individual before treatment with the anti-Cls antibody. In some modalities, administering a humanized anti-Cls antibody of the present description to an individual reduces glial cell activation in that individual. For example, in some modalities, an anti-Cls antibody of the present description, when administered in one or more doses as monotherapy or in combination therapy to an individual with a complement-mediated disease or disorder, reduces glial cell activation in that individual by at least approximately 10%, at least approximately 15%, at least approximately 20%, at least approximately 25%, at least approximately 30%, at least approximately 40%, at least approximately 50%, at least approximately 60%, at least 115 around 70%, at least around 80%, at least around 90%, or more than 90%, compared to glial cell activation in the individual before anti-Cls antibody treatment. In some modalities, the glial cells are astrocytes or microglia. In some cases, administering a humanized anti-Cls antibody as described here to an individual reduces lymphocyte infiltration in that individual. UO3 For example, in some modalities, an anti-Cls antibody of the present, when administered in one or more doses as monotherapy or in combination therapy to an individual having a complement-mediated disease or disorder, reduces lymphocyte infiltration in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to the lymphocyte infiltration in the individual before treatment with the anti-Cls antibody. In some modalities, administering a humanized anti-Cls antibody as described herein to an individual reduces macrophage infiltration in that individual. For example, in some modalities, an anti-Cls antibody 116 humanized from the present description, when administered in one or more doses as monotherapy or in combination therapy to an individual having a complement-mediated disease or disorder, reduces macrophage infiltration in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to the macrophage infiltration in the individual before treatment with the anti-Cls antibody. In some regimens, administering a humanized anti-Cls antibody of the present description to an individual reduces antibody deposition in that individual. For example, in some regimens, a humanized anti-Cls antibody of the present description, when administered in one or more doses as monotherapy or in combination therapy to an individual with a complement-mediated disease or disorder, reduces antibody deposition in that individual by at least approximately 10%, at least approximately 15%, at least approximately 20%, at least approximately 25%, at least approximately 30%, at least approximately 40%, at least approximately 50%, at least approximately 60%, at least approximately 70%, at least 117 around 80%, at least around 90%, or more than 90%, compared to the antibody deposition in the individual before treatment with the anti-Cls antibody. In some formulations, administering an anti-Cls antibody of the present description to an individual reduces the production of anaphylatoxins (e.g., C3a, C4a, C5a) in that individual. For example, in some formulations, a humanized anti-Cls antibody of the present description, when administered in one or more doses as monotherapy or in combination therapy to an individual with a complement-mediated disease or disorder, reduces anaphylatoxin production in that individual by at least IVIA / a / ZUZZ / UU I UO3 around 10%, at least around 15%, at least around 20%, at least around 25%, at least around 30%, at least around 40%, at least around 50%, at least around 60%, at least around 70%, at least around 80%, at least around 90%, or more than 90%, compared to the level of anaphylatoxin production in the individual before treatment with the anti-Cls antibody. • This description provides for the use of a humanized anti-Cls antibody of this description or a pharmaceutical composition comprising a humanized anti-Cls antibody of this description and an excipient. pharmaceutically acceptable for treating an individual who has 118 a complement-mediated disease or disorder. In some embodiments, this description provides for the use of a humanized anti-Cls antibody of this description to treat an individual who has a complement-mediated disorder or disease. In some embodiments, this description provides for the use of a pharmaceutical composition comprising a humanized anti-Cls antibody of this description and a pharmaceutically acceptable excipient to treat an individual who has a complement-mediated disorder or disease. This description provides for the use of a humanized anti-Cls antibody of this description in the preparation of a medicament for the treatment of an individual who has a complement-mediated disorder or disease. This description provides for the use of a humanized anti-Cls antibody of this description or a pharmaceutical composition comprising a humanized anti-Cls antibody of this description and a pharmaceutically acceptable excipient for inhibiting complement activation. In some embodiments, this description provides for the use of a humanized anti-Cls antibody of this description or a pharmaceutical composition comprising a humanized anti-Cls antibody of this description and an excipient. 119 pharmaceutically acceptable for inhibiting complement activation in an individual having a complement-mediated disease or disorder. In some embodiments, this description provides for the use of a humanized anti-Cls antibody of this description to inhibit complement activation in an individual having a complement-mediated disorder or disease. In some embodiments, this description provides for the use of a pharmaceutical composition comprising a humanized anti-Cls antibody of this description and a pharmaceutically acceptable excipient to inhibit complement activation in an individual having a complement-mediated disorder or disease. This description provides for the use of a humanized anti-Cls antibody described herein in the formulation of a medicament to modulate complement activation. In some formulations, the medicament inhibits complement activation in an individual. UO3 who has a complement-mediated disorder or disease. This description provides a humanized anti-Cls antibody of the present description or a pharmaceutical composition comprising a humanized anti-Cls antibody of the present description and a pharmaceutically acceptable excipient for use in medical therapy. In some In 120 embodiments, this description provides a humanized anti-Cls antibody of the present description for use in medical therapy. In some embodiments, this description provides a pharmaceutical composition comprising a humanized anti-Cls antibody of the present description and a pharmaceutically acceptable excipient for use in medical therapy. This description provides a humanized anti-Cls antibody of this description or a pharmaceutical composition comprising a humanized anti-Cls antibody of this description and a pharmaceutically acceptable excipient for the treatment of an individual with a complement-mediated disease or disorder. In some embodiments, this description provides a humanized anti-Cls antibody of this description for the treatment of an individual with a complement-mediated disorder or disease. In some embodiments, this description provides a pharmaceutical composition comprising a humanized anti-Cls antibody of this description and a pharmaceutically acceptable excipient for the treatment of an individual with a complement-mediated disorder or disease. This description provides a humanized anti-Cls antibody of the present description or a pharmaceutical composition comprising a humanized anti-Cls antibody UO3 121 of the present description and a pharmaceutically acceptable excipient for modulating complement activation. In some embodiments, the present description provides a humanized anti-Cls antibody of the present description for modulating complement activation. In some embodiments, the present description provides a pharmaceutical composition comprising a humanized anti-Cls antibody of the present description and a pharmaceutically acceptable excipient for modulating complement activation. In some embodiments, the anti-Cls antibody inhibits complement activation. EXAMPLES The following examples are provided to give those skilled in the art a complete description of how to carry out and use the present invention and are not intended to limit the scope of what the inventors consider to be the invention, nor are they intended to establish that the experiments below are all or the only experiments performed. Every attempt has been made to ensure the accuracy of the numbers used (e.g., quantities, temperatures, etc.), but a margin of error and experimental deviation should be considered. Unless otherwise stated, parts are parts by weight, molecular weight is the average molecular weight, temperature is in degrees Celsius, and pressure is atmospheric or similar. 122 Use standard abbreviations, for example bp, base pair or pairs; kb, kilobase / s; pl, picoliter / s; sec, second / s; min, minute / s; h, hour / s; aa, amino acid / s; kb, kilobase / s; bp, base pair or pairs; nt, nucleotide / s; im, intramuscular or by intramuscular route; ip, intraperitoneal or by intraperitoneal route; sc, subcutaneous or by subcutaneous route and the like. Example 1: Humanized TNT005 variants Humanized variants of TNT005 were generated. The amino acid sequences of the heavy chain VH domains of humanized variants 1–5 are also provided, as are the nucleotide sequences encoding the heavy chain VH domain of the humanized variants. The amino acid sequences of the light chain VL domain of humanized variants 1, 2, and 5, and the nucleotide sequences encoding the light chain VL domain of the humanized variants, are shown in Figures 6–8. Amino acid differences related to the amino acid sequence of TNT005 (VL SEQ ID NO: 7; VH SEQ ID NO: 8) are summarized in Tables 2 and 3 (Figure 9 and Figure 10, respectively). The single-letter amino acid codes are shown below (with 3-letter amino acid codes in parentheses): G - Glycine (Gly) P - Proline (Pro) IVIA / a / ZUZZ / UU I UO3 123 A - Alanine (Ala) V - Valine (Val) L - Leucine (Leu) I - Isoleucine (lie) M - Methionine (Met) C - Cysteine ​​(Cys) F - Phenylalanine (Phe) Y - Tyrosine (Tyr) W - Tryptophan (Trp) H - Histidine (His) K - Lysine (Lys) R - Arginine (Arg) Q - Glutamine (Gln) N - Asparagine (Asn) E - Glutamic acid (Glu) D - Aspartic acid (Asp) S - Serine (Be) T - Threonine (Thr) Example 2: Characterization of humanized TNT005 variants The binding characteristics of humanized TNT005 variants are provided in Tables 4 and 5 (Figure 11 and Figure 12, respectively). The relative binding affinities for various humanized TNT005 variants with respect to activated Cls are provided in Table 4 (first column of IVIA / a / ZUZZ / UU I UO3 124 data), which is presented in FIGURE 11. All 15 combinations were produced (VH variant 1 + Vk variant 1; VH variant 1 + Vk variant 2; VH variant 1 + Vk variant 5; VH variant 2 + Vk variant 1; VH variant 2 + Vk variant 2; VH variant 2 + Vk variant 5; VH variant 3 + Vk variant 1; VH variant 3 + Vk variant 2; VH variant 3 + Vk variant 5; VH variant 4 + Vk variant 1; VH variant 4 + Vk variant 2; VH variant 4 + Vk variant 5; VH variant 5 + Vk variant 1; VH variant 5 + Vk variant 2; VH variant 5 + Vk variant 5). Each humanized variant was evaluated to see its ability to compete with biotinylated TNT005 for binding to active Cls. The data are illustrated in FIGURE 11, second data column. Each humanized variant was evaluated in a commercially available assay that measures activation of the classical complement (CP) pathway. The results are shown in Figure 11, third column of data. The data show that all 15 humanized variants inhibit CP activation with an IC50 similar to that of TNT005. Kinetic characterization of binding affinity was performed on 8 of the humanized TNT005 variants. The data are described in Table 5, which is presented in Figure 12. 125 Example 3: In vivo studies in cynomolgus monkeys To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) properties of humanized TNT005, single-dose and repeated-dose studies were conducted in cynomolgus monkeys (Macaca fascicularis). Additionally, to compare the bioavailability of humanized TNT005 via various routes of administration, the humanized variant was administered by intravascular (IV) or subcutaneous (SC) injection. Following dosing of humanized TNT005, plasma and serum samples were collected at designated time points to determine circulating concentrations (PK) of humanized TNT005 and to assess the inhibition of the classical complement pathway (PD) by humanized TNT005. All study animals were female, weighed between 2.4 and 3.9 kg, and were between 3 and 5 years old. Additionally, all animals had not received any prior treatment before receiving the pharmaceutical dosage. The study consisted of two parts: 1) Phase 1 - a unit-dose study comparing the PK / PD of humanized TNT005 in vehicle control (no drug administered), low-dose and high-dose groups by intravenous (IV) administration and a coincidentally high-dose humanized TNT005 group administered subcutaneously (SC); and 126 2) Phase 2 - a low-dose multiple-dose SC group (daily for 7 days). The Phase 1 study design consisted of four animal groups, three of which were dosed with humanized TNT005 (n=4 animals / dose cohort), and the fourth with vehicle control (phosphate-buffered saline; n=3 animals). Animals dosed intravenously (IV) received a bolus injection into a peripheral vein, while the subcutaneous (SC) injection was administered in the interscapular region of the back. Group 1 was designated the control group and received the IV vehicle. Groups 2 and 3 received a single IV dose of humanized TNT005 at 10 mg / kg and 45 mg / kg, respectively. Finally, group 4 received a single SC dose at 45 mg / kg to directly compare SC bioavailability with the corresponding IV group (group 3). Table 6 summarizes the Phase 1 study design. Table 6 IVIA / a / ZUZZ / UU I UO3 Group Test Article Route Dose Level (mg / kg) Dose Concentration (mg / mL) Dose Volume (mL / kg) Number of Female Animals 1 Vehicle IV 0 0 4.5 3 2 TNT005 humanized IV 10 2.2 4.5 4 3 TNT005 humanized IV 45 10 4.5 4 4 TNT005 humanized SC 45 10 4.5 4 Whole blood was drawn into K2EDTA tubes and serum separator tubes for plasma and serum processing, respectively, and immediately stored at -15°C to 25°C. Sample collections occurred before and after dosing with humanized TNT005 or vehicle control according to the schedule described in Table 7. Table 7 Group Blood Collections (hours post-dose) Blood Volume Collection Tube / Additive / Processing Aliquots / Storage All Pre-dose, 0.25, 0.5, 1, 4, 8, 12, 24, 48, 72, 96, 120, 168, 240, 336, 432, and 504 (Day 22) hours post-dose. Additionally, samples were collected daily on Days 23 to 43 post-dose. At least 1.3 mL SST (~0.7 mL) / Centrifuge per SOP 1 x 350 pL -15 to -25°C K2EDTA (~0.6 mL) on ice / Centrifuge at 2 to 8°C 1 x 300 pL 15 to -25°C 128 The Phase 2 study was designed to evaluate the PK / PD ratio of repeated low-dose humanized TNT005 administered subcutaneously. Phase 2 animals were appropriated from the Phase 1 control group (n=3) plus one animal from the low-dose Group IV (Group 1). Phase 2 animals were dosed daily with 4 mg / kg of humanized TNT005 subcutaneously for 7 days. Phase 2 animals were dosed 57 days after the Phase 1 dosing. Table 8 summarizes the Phase 2 study design. Table 8 ML / a / ZUZZ / UU I UO3 Group Test Article Route Dose Level (mg / kg) Dose Concentration (mg / mL) Dose Volume (mL / kg) 1 TNT005 Humanized SC 4 0.9 4.5 Whole blood was drawn into K2EDTA tubes and serum separator tubes for plasma and serum processing, respectively, and immediately stored at -15°C to -25°C. Sample collections occurred before and after dosing with humanized TNT005 according to the schedule described in Table 9. 129 Table 9 - Phase 2 Blood Extraction Scheduling IVIA / S / ZUZZ / UU I UO3 entire Group Blood Draws (hour after dose) Blood Volume Collection Tube / Additive / Processing Aliquots / Storage 1 Day 1: Pre-dose, then 1.5, 2, 3, 4, 6, 10, 12, and 24 hours post-dose (pre-dose on day 2) Days 3 to 6: Pre-dose Day 7: Pre-dose, then 1.5, 4, 8, 12, 24, and 48 hours post-dose At least 1.3 mL SST (~0.7 mL) / Centrifuge per SOP 1 x 350 pL -15 to -25°C K2EDTA (~0.6 mL) on ice / Centrifuge at 2 to 8 °C 1 x 300 pL 15 to -25°C 130 Results Phase 1 Pharmacokinetics and pharmacodynamics To evaluate the pharmacokinetic profile of humanized TNT005 in Phase 1, plasma samples collected at the time points specified in Table 7 were diluted and tested using an ELISA to quantify plasma concentrations of humanized TNT005. Briefly, the diluted plasma samples were added to a 96-well plate pre-coated with activated Cls. After incubation and subsequent washing of the plasma sample, a human IgG-specific horseradish peroxidase-conjugated detection antibody was added to detect humanized TNT005 bound to Cls. Finally, 3,3',5,5'-tetramethylibencidin (TMB) substrate was added to initiate a colorimetric reaction, which was read using a spectrophotometer. By interpolating from a humanized TNT005 standard curve in parallel with the plasma samples, the plasma concentrations of humanized TNT005 were determined for all samples.The results of the Phase 1 pharmacokinetic analyses of the study are shown in FIGURE 14 (Day 1-43) and FIGURE 15 (Day 32-43). Following IV administration, the plasma PK profiles of humanized TNT005 exhibited a typically elevated Cmax followed by dose-dependent clearance. SC administration resulted in an absorption phase, which resulted in a 131 Overall lower Cmax was delayed compared to the matched IV dose cohort. The clearance rate of humanized TNT005 in the 45 mg / kg IV and SC dose groups was compared from 72 hours to the end of the study. Figure 14 describes the pharmacokinetic profile of humanized TNT005 in cynomolgus monkeys dosed during Phase 1 (Day 1–Day 43). The dosage groups received either the vehicle; 10 mg / kg (MPK) of humanized TNT005 IV; 45 MPK of humanized TNT005 IV; or 45 MPK of humanized TNT005 SC. The mean plasma concentrations of humanized TNT005 for each dosage group (n = 4 animals / cohort of humanized TNT005) are plotted as a function of time post-dose. Figure 15 describes pharmacokinetic profiles of humanized TNT005 in cynomolgus monkeys dosed in Phase 1 (Day 32-Day 43). The dose groups were as in Figure 14. The average plasma concentrations of humanized TNT005 for each dose group (n = 4 animals / cohort of humanized TNT005) are plotted as a function of time post-dose. The pharmacodynamic effects of humanized TNT005 were evaluated using the Wieslab® Classic Complement Pathway Kit. The Wieslab® Kit is commercially available and involves the use of an enzyme-linked immunosorbent assay (ELISA) designed to evaluate the IVIA / a / ZUZZ / UU I UO3 132 The strength of classical complement pathway activity in serum samples was assessed by activating the classical pathway ex vivo and measuring the ex vivo generation of the pathway's end-cleavage product, C5b-9. Samples were evaluated according to the manufacturer's instructions. Briefly, serum samples from monkeys, collected at the times shown in Table 7, were diluted and added to the wells of the provided 96-well plate. After incubation, a detection antibody specific for the classical pathway's end-cleavage product, C5b-9, was added, and the colorimetric reaction was measured using a spectrophotometer. All samples for an individual monkey were compared and normalized to the pre-dose sample from the same monkey (pre-dose = 100% activity). The results for the pharmacodynamic readout in the Phase 1 groups are shown in Figure 16.Intravenous administration of humanized TNT005 resulted in near-complete to complete inhibition of the classical pathway in both dose groups immediately after dosing. Recovery of classical pathway activity was gradual and dose-dependent, with animals in the 45 mg / kg dose cohorts recovering more slowly than those in the 10 mg / kg cohort. The IV and subcutaneous groups dosed at 45 mg / kg showed very similar recovery times for pathway activity, consistent with the profiles. 133 pharmacokinetics of humanized TNT005 similar for those groups (FIGURE 14). Figure 16 describes the classical pathway activity (PD reading) of serum samples from cynomolgus monkeys dosed in Phase 1 (Day 1–Day 43). The dose groups received the vehicle; 10 mg / kg (MPK) of humanized TNT005 IV; 45 MPK of humanized TNT005 IV; or 45 MPK of TNT005 humanized SC. The activity of the classical pathway for each dose group (normalized to pre-dose activity; n = 4 animals / group TNT005 humanized) is plotted as a function of time after the dose. Phase 2 Pharmacokinetics (PK) and pharmacodynamics (PD) The pharmacodynamics and pharmacokinetics of humanized TNT005 in Phase 2 were evaluated in the same manner as described in Phase 1. The results of the Phase 2 pharmacokinetic and pharmacodynamic analyses are shown in Figure 17. Subcutaneous administration of low-dose humanized TNT005 (4 mg / kg) resulted in a slow absorption phase within the first 24 hours of dosing (Figure 17, red graph, right y-axis). Along with the increase in plasma concentrations of humanized TNT005, the activity of the classical serum pathway decreased (Figure 17, blue graph, left y-axis). Repeated daily dosing at 4 mg / kg resulted in a gradual increase in plasma humanized TNT005 and reduced activity of the classical serum pathway. 134 Additionally, serum classical pathway activity was reduced to 10% of pre-dose levels by day 7 (i.e., -90% classical pathway inhibition). Figure 17 describes a PK / PD profile of humanized TNT005 in cynomolgous monkeys dosed in Phase 2 (SC administration of 4 mg / kg daily for 7 days). Average plasma concentrations of humanized TNT005 (right y-axis) and average serum classical pathway activity (left y-axis) were plotted against time for Phase 2 (n=4 animals). Although the present invention has been described with reference to its specific embodiments, those skilled in the art will understand that various changes can be made and that equivalents can be substituted without departing from the true spirit and scope of the invention. Furthermore, many modifications can be made to adapt a particular situation, material, composition, process, or process step or steps to the objective, spirit, and scope of the present invention. All such modifications are intended to be included within the scope of the appended claims. It is hereby stated that, as of this date, the best method known to the applicant for putting the aforementioned invention into practice is the one that is clear from the present description of the invention.

Claims

1. A nucleic acid or nucleic acids encoding a humanized antibody that binds specifically to complement component Cls, characterized in that the humanized antibody comprises: a) a VH region comprising the amino acid sequence: (Q / E)VQL(V / Q)QSGAE(V / L)KKPGASVK(L / V)SC(T / A)ASGFNIKD DYIHWV(K / R)QAPGQGLEWIGRIDPADGHTKYAPKFQVK(V / A)TITADTST(S / N)TAY (L / M)(E / Q)LSSL(R / T)SEDTAVYYCARYGYGREVFDYWGQGTTVTVSS (SEQ ID NO: 26); and b) a VL region comprising the amino acid sequence: DIVLTQSPDSLAVSLGERATISCKASQSVDYDGDSYMNWYQQK(T / P)GQP PK(I / L)LIYDASNLESGIPARFSGSGSGTDFTLTISSLE(E / P)EDFA(l / V)YYCQQSN EDPWTFGGGTKVEIK (SEQ ID NO: 27).

2. The nucleic acid or nucleic acids according to claim 1, characterized in that the humanized antibody is a Fab fragment, an F(ab')2 fragment, an scFv, or an Fv.

3. The nucleic acid or nucleic acids of claim 1, characterized in that the humanized antibody comprises a heavy chain constant region of the IgG1, IgG2, IgG3, or IgG4 isotype.

4. The nucleic acid or nucleic acids according to claim 1, characterized in that the humanized antibody is selected from the group consisting of: a) an antibody comprising a VH region comprising the amino acid sequence set out in SEQ ID NO: 14 and a VL region comprising the amino acid sequence set out in SEQ ID NO: 22; b) an antibody comprising a VH region comprising the amino acid sequence set out in SEQ ID NO: 10 and a VL region comprising the amino acid sequence set out in SEQ ID NO: 20; c) an antibody comprising a VH region comprising the amino acid sequence set out in SEQ ID NO: 10 and a VL region comprising the amino acid sequence set out in SEQ ID NO: 22;d) an antibody comprising a VH region comprising the amino acid sequence specified in SEQ ID NO: 10 and a VL region comprising the amino acid sequence specified in SEQ ID NO: 24; e) an antibody comprising a VH region comprising the amino acid sequence specified in SEQ UO3 137 ID NO: 12 and a VL region comprising the amino acid sequence specified in SEQ ID NO: 20; f) an antibody comprising a VH region comprising the amino acid sequence specified in SEQ ID NO: 12 and a VL region comprising the amino acid sequence specified in SEQ ID NO: 22; g) an antibody comprising a VH region comprising the amino acid sequence specified in SEQ ID NO: 12 and a VL region comprising the amino acid sequence specified in SEQ ID NO: 24;(h) an antibody comprising a VH region comprising the amino acid sequence specified in SEQ ID NO: 14 and a VL region comprising the amino acid sequence specified in SEQ ID NO: 20; (i) an antibody comprising a VH region comprising the amino acid sequence specified in SEQ ID NO: 14 and a VL region comprising the amino acid sequence specified in SEQ ID NO: 24; (j) an antibody comprising a VH region comprising the amino acid sequence specified in SEQ ID NO: 16 and a VL region comprising the amino acid sequence specified in SEQ ID NO: 20; (k) an antibody comprising a VH region comprising the amino acid sequence specified in SEQ ID NO: 16 and a VL region comprising the 138-amino-acid sequence specified in SEQ ID NO: 22;(1) an antibody comprising a VH region comprising the amino acid sequence specified in SEQ ID NO: 16 and a VL region comprising the amino acid sequence specified in SEQ ID NO: 24; (m) an antibody comprising a VH region comprising the amino acid sequence specified in SEQ ID NO: 18 and a VL region comprising the amino acid sequence specified in SEQ ID NO: 20; (n) an antibody comprising a VH region comprising the amino acid sequence specified in SEQ ID NO: 18 and a VL region comprising the amino acid sequence specified in SEQ ID NO: 22; (i) an antibody comprising a VH region comprising the amino acid sequence specified in SEQ ID NO: 18 and a VL region comprising the amino acid sequence specified in SEQ ID NO:

24.

5. The nucleic acid or nucleic acids according to claim 4, characterized in that the humanized antibody is a Fab fragment, an F(ab')2 fragment, an scFv, or an Fv.

6. The nucleic acid or nucleic acids according to claim 4, characterized in that the humanized antibody comprises a heavy chain constant region of the IgG1, IgG2, IgG3, or IgG4 isotype. UO3 139 7. A nucleic acid or nucleic acids encoding a humanized antibody that binds specifically to complement component Cls, characterized in that the antibody comprises a VH region comprising the amino acid sequence set out in SEQ ID NO:14 and a VL region comprising the amino acid sequence set out in SEQ ID NO:

22.

8. The nucleic acid or nucleic acids according to claim 7, characterized in that the humanized antibody comprises a heavy chain constant region of the IgG4 isotype.

9. An expression vector, characterized in that it comprises the nucleic acid or nucleic acids according to claim 1.

10. A cloning vector, characterized in that it comprises the nucleic acid or nucleic acids according to claim 1.

11. A recombinant cell, characterized in that it comprises the nucleic acid or nucleic acids according to claim 1.

12. The recombinant cell according to claim 11, characterized in that the recombinant cell is a recombinant mammalian cell.

13. A recombinant cell, characterized in that it comprises the expression vector in accordance with claim 9 of UO3 140.

14. The recombinant cell according to claim 13, characterized in that the recombinant cell is a recombinant mammalian cell.

15. A method for producing a humanized antibody that binds specifically to complement component Cls, the method being characterized in that it comprises expressing the expression vector according to claim 9 in a recombinant cell.

16. The method according to claim 15, characterized in that the recombinant cell is a recombinant mammalian cell.

17. An expression vector, characterized in that it comprises the nucleic acid or nucleic acids according to claim 7.

18. A cloning vector, characterized in that it comprises the nucleic acid or nucleic acids according to claim 7.

19. A recombinant cell, characterized in that it comprises the nucleic acid or nucleic acids according to claim 7.

20. The recombinant cell according to claim 18, characterized in that the recombinant cell is a recombinant mammalian cell.

21. A recombinant cell, characterized in that IVIA / a / ZUZZ / UU I UO3 141 comprises the expression vector according to claim 17.

22. The recombinant cell according to claim 21, characterized in that the recombinant cell 5 is a recombinant mammalian cell.

23. A method for producing a humanized antibody that binds specifically to complement component Cls, the method being characterized in that it comprises expressing the expression vector according to claim 17 in a recombinant cell.

24. The method according to claim 23, characterized in that the recombinant cell is a recombinant mammalian cell.