Antibodies specifically recognizing c5a and uses thereof

Abstract

The present application relates to an antibody specifically recognizing complement component 5a (C5a), which has higher C5a binding activity and weaker C5 binding activity, and can avoid high concentration and / or frequent administration of anti-C5a antibody. It also relates to a nucleic acid sequence encoding the above antibody, a vector and cell containing the nucleic acid sequence, a pharmaceutical composition containing the antibody, and the use of the anti-C5a antibody in the preparation of a medicament for treating autoimmune diseases, inflammation, cancer, pain, respiratory and / or transplantation related diseases.

Description

[0001] Cross-references to related applications

[0002] This application claims priority to Chinese Patent Application No. 202110762546.0, filed on July 6, 2021, entitled "Antibody that specifically recognizes C5A and its application", the entire contents of which are incorporated herein by reference.

[0003] Submitting sequence lists as ASCII text files

[0004] The contents of the following submitted ASCII TEXT text file are incorporated herein by reference in their entirety: Sequence List in Computer-Readable Form (CRF) (Text name: CN_202106216389_SEQLIST.txt, Record date: 2021.06.21, Size: 79KB). Technical Field

[0005] This application relates to antibodies that specifically recognize complement component 5a (C5a), methods for their preparation, and uses, including uses for the treatment of autoimmune diseases, inflammation, cancer, pain, respiratory and / or transplant-related diseases. Background Technology

[0006] C5a is an active peptide involved in allergic reactions and inflammation. It is formed by the cleavage of complement component C5 by C5 convertase in the complement cascade. C5a stimulates mast cell degranulation, the release of tumor necrosis factor-α (TNF-α) and histamine, and also recruits phagocytes to sites of infection and inflammation by increasing the expression of adhesion molecules on the surface of endothelial cells (Mollnes, TE et al. Blood 2002, 100, 1869–1877; Riedemann, NC et al. Immunity 2003, 19, 193–202). In certain pathological conditions, such as post-transplant rejection and asthma, C5a also leads to increased vascular permeability (Gueler, F. et al. J. Am. Soc. Nephrol. 2008, 19, 2302–2312; Krug, N. et al. Am. J. Respir. Crit. Care Med. 2001, 164, 1841–1843; Khan, MA et al. Proc. Natl. Acad. Sci. USA 2013, 110, 6061–6066). Serum C5a levels have been discussed in several studies. In a study by Lechner et al., the C5a level in the control group was 8.34 ± 2.05 (ng / mL) (Lechner, J. et al. Immun. Ageing 2016, 13, 4). Other studies have shown that, under normal circumstances, plasma C5a levels are very low due to the rapid clearance of anaphylactic toxins (Oppermann, M. et al. Immunology 1994, 82, 516–521). Treatment with C5a (25 nM) increased the level of transforming growth factor-β (TGF-β) in mouse cortical renal tubular cells, indicating that C5a can lead to renal fibrosis and renal scarring (Boor, P. et al. J. Am. Soc. Nephrol. 2007, 18, 1508–1515).

[0007] C5a is a potent pro-inflammatory molecule that binds to a classic G protein-coupled receptor (GPCR) C5aRI (CD88) and triggers activation of pro-inflammatory signaling pathways (Li, R. et al. FASEB J. 2013, 27, 855–864). C5aR is widely expressed in non-myeloid cells, such as umbilical vascular endothelial cells (HUVECs), and in the dermis, liver, lung, and proximal tubules of the kidneys in mice (Monsinjon, T. et al. FASEB J. 2003, 17, 1003–1014; Gerard, C. et al. Annu. Rev. Immunol. 1994, 12, 775–808; Haviland, D. Let al. J. Immunol. 1995, 154, 1861–1869). Furthermore, studies have shown that C5aR is expressed in glomerular endothelial cells rather than podocytes, suggesting that C5a may primarily cause proteinuria in renal endothelial cells (Tsai, I. Jetal. Cell. Mol. Life Sci. 2015, 72, 3157–3171).

[0008] Therefore, neutralizing C5a and blocking its binding to C5aR has become a method for treating C5a-mediated diseases and symptoms. Patent application WO2011063980 A1 discloses the antibody INab308 (InflaRx) targeting human C5a, WO2012088247 A1 discloses the C5a antibody MEDI-7814 (MedImmune), and patent US10450370 B2 discloses the C5a antibody BNJ383 (Alexion).

[0009] All publications, patents, patent applications, and disclosed information in published patent applications mentioned herein are incorporated herein by reference in their entirety.

[0010] Application Overview

[0011] In some embodiments, a separate anti-C5a antibody is provided, comprising a heavy chain variable domain (V... H ), the V HIt includes: a heavy chain complementarity determination region (HC-CDR)1, which contains X1LSX2H (SEQ ID NO:70), wherein X1 is D or E, and X2 is I or M; HC-CDR2, which contains GFX1PX2X3GX4TIYAQNFQG (SEQ ID NO:71), wherein X1 is A, D, E, G, L, N, P, Q, S, V or Y, X2 is D, E, F, I, L, N, R, S, T or V, X3 is A, D, F, I, L, N, Q or S, and X4 is D, G, T or V; and HC-CDR3, which contains GISX1X2X3NDAFDI (SEQ ID NO:74), wherein X1 is D, E or S, X2 is A, G, I, V or W, and X3 is H or W; and a light chain variable structural domain (V L ), the V L It includes: a light chain complementarity determination region (LC-CDR)1, which includes RASQSVX1SX2YLA (SEQ ID NO: 77), wherein X1 is K or S and X2 is N, R or S; LC-CDR2, which includes DASX1RX2T (SEQ ID NO: 78), wherein X1 is A, D, E or S and X2 is A, D or S; and LC-CDR3, which includes QQYYX1X2PX3T (SEQ ID NO: 79), wherein X1 is A, D or I, X2 is L, P or S and X3 is I, L or T.

[0012] In some embodiments, an isolated anti-C5a antibody is provided, which comprises V H The V H Contains: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-3 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:6-31 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:38-44 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; and V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:48-50 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:54-58 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:62-66 or variants thereof, the variants comprising substitutions of up to about 3 amino acids.

[0013] In some embodiments, an isolated anti-C5a antibody is provided, comprising: V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:80-109 H Includes HC-CDR1, HC-CDR2, and HC-CDR3, as well as V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:118-124 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0014] In some embodiments, an isolated anti-C5a antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:80. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:118. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (ii)V H It contains V as shown in the amino acid sequence SEQ ID NO:81. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:118. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iii)V H It contains V as shown in the amino acid sequence SEQ ID NO:82. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:118. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iv)V H It contains V as shown in the amino acid sequence SEQ ID NO:83. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:119. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (v)V HIt contains V as shown in the amino acid sequence SEQ ID NO:84. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:120. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (vi)V H It contains V as shown in the amino acid sequence SEQ ID NO:85. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:118. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (vii)V H It contains V as shown in the amino acid sequence SEQ ID NO:86. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:121. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (viii)V H It contains V as shown in the amino acid sequence SEQ ID NO:87. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (ix)V H It contains V as shown in the amino acid sequence SEQ ID NO:88. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:123. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (x)V H It contains V as shown in the amino acid sequence SEQ ID NO:89. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:124. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xi)VH It contains V as shown in the amino acid sequence SEQ ID NO:90. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xii)V H It contains V as shown in the amino acid sequence SEQ ID NO:91. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (xiii)V H It contains V as shown in the amino acid sequence SEQ ID NO:92. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xiv)V H It contains V as shown in the amino acid sequence SEQ ID NO:93. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xv)V H It contains V as shown in the amino acid sequence SEQ ID NO:94. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xvi)V H It contains V as shown in the amino acid sequence SEQ ID NO:95. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. LIncludes LC-CDR1, LC-CDR2, and LC-CDR3; (xvii)V H It contains V as shown in the amino acid sequence SEQ ID NO:96. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xviii)V H It contains V as shown in the amino acid sequence SEQ ID NO:97. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xix)V H It contains V as shown in the amino acid sequence SEQ ID NO:98. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (xx)V H It contains V as shown in the amino acid sequence SEQ ID NO:99. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xxi)V H It contains V as shown in the amino acid sequence SEQ ID NO:100. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (xxii)V H It contains V as shown in the amino acid sequence SEQ ID NO:101. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122.L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (xxiii)V H It contains V as shown in the amino acid sequence SEQ ID NO:102. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (xxiv)V H It contains V as shown in the amino acid sequence SEQ ID NO:103. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xxv)V H It contains V as shown in the amino acid sequence SEQ ID NO:104. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xxvi)V H It contains V as shown in the amino acid sequence SEQ ID NO:105. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xxvii)V H It contains V as shown in the amino acid sequence SEQ ID NO:106. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xxviii)V H It contains V as shown in the amino acid sequence SEQ ID NO:107. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V LIt contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xxix)V H It contains V as shown in the amino acid sequence SEQ ID NO:108. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; or (xxx)V H It contains V as shown in the amino acid sequence SEQ ID NO:109. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0015] In some embodiments, an isolated anti-C5a antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:6; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:38, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:62, or the V L (ii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:6; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V LContains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:62, or the V L (iii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:7; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:62, or the V L (iv) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:40, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:63, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (v)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:9; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The VL Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:64, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (vi)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:41, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:62, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (vii)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:11; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:55; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (viii)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (ix)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:13; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:49; LC-CDR2, which contains the amino acid sequence SEQ ID NO:57; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (x)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:14; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:50; LC-CDR2, which contains the amino acid sequence SEQ ID NO:58; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:66, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (xi)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:15; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V HVariants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (xii)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:16; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (xiii)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:17; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L Variants of this type contain up to about 5 amino acid substitutions in their LC-CDRs; (xiv)V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:18; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs; (xv)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:19; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs; (xvi)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:42, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs; (xvii)V HThe V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:43, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (xviii)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:44, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L Variants of this type contain up to about 5 amino acid substitutions in their LC-CDRs; (xix)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:20; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V LThe variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (xx)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:21; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (xxi)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:22; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (xxii)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:23; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V LContains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (xxiii)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:24; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (xxiv)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:25; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs; (xxv)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:26; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (xxvi)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:27; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (xxvii)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:28; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (xxviii)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:29; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V HVariants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (xxix)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:30; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L Variants whose LC-CDRs contain substitutions of up to about 5 amino acids; or (xxx)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:31; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0016] In some embodiments, any of the isolated anti-C5a antibodies described above, the isolated anti-C5a antibody comprising: V HIt comprises any of the amino acid sequences shown in SEQ ID NOs:80-109 or variants thereof, said variants having at least about 90% sequence identity with any of the amino acid sequences shown in SEQ ID NOs:80-109; and V L It comprises any of the amino acid sequences shown in SEQ ID NOs:118-124 or variants thereof, wherein the variants have at least about 90% sequence identity with any of the amino acid sequences shown in SEQ ID NOs:118-124.

[0017] In some embodiments, an isolated anti-C5a antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:80 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:80; and V L It contains the amino acid sequence SEQ ID NO:118 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:118; (ii) V H It comprises the amino acid sequence SEQ ID NO:81 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:81; and V L It contains the amino acid sequence SEQ ID NO:118 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:118; (iii) V H It comprises the amino acid sequence SEQ ID NO:82 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:82; and V L It contains the amino acid sequence SEQ ID NO:118 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:118; (iv)V H It comprises the amino acid sequence SEQ ID NO:83 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:83; and V L It contains the amino acid sequence SEQ ID NO:119 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:119; (v)V H It comprises the amino acid sequence SEQ ID NO:84 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:84; and V LIt contains the amino acid sequence SEQ ID NO:120 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:120; (vi)V H It comprises the amino acid sequence SEQ ID NO:85 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:85; and V L It contains the amino acid sequence SEQ ID NO:118 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:118; (vii)V H It comprises the amino acid sequence SEQ ID NO:86 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:86; and V L It contains the amino acid sequence SEQ ID NO:121 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:121; (viii)V H It comprises the amino acid sequence SEQ ID NO:87 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:87; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (ix)V H It comprises the amino acid sequence SEQ ID NO:88 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:88; and V L It contains the amino acid sequence SEQ ID NO:123 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:123; (x)V H It comprises the amino acid sequence SEQ ID NO:89 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:89; and V L It contains the amino acid sequence SEQ ID NO:124 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:124; (xi)V H It comprises the amino acid sequence SEQ ID NO:90 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:90; and V LIt contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xii)V H It comprises the amino acid sequence SEQ ID NO:91 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:91; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xiii)V H It comprises the amino acid sequence SEQ ID NO:92 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:92; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xiv)V H It comprises the amino acid sequence SEQ ID NO:93 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:93; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xv)V H It comprises the amino acid sequence SEQ ID NO:94 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:94; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xvi)V H It comprises the amino acid sequence SEQ ID NO:95 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:95; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xvii)V H It comprises the amino acid sequence SEQ ID NO:96 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:96; and V LIt contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xviii)V H It comprises the amino acid sequence SEQ ID NO:97 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:97; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xix)V H It comprises the amino acid sequence SEQ ID NO:98 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:98; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xx)V H It comprises the amino acid sequence SEQ ID NO:99 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:99; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xxi)V H It comprises the amino acid sequence SEQ ID NO:100 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:100; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xxii)V H It comprises the amino acid sequence SEQ ID NO:101 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:101; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xxiii)V H It comprises the amino acid sequence SEQ ID NO:102 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:102; and V LIt contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xxiv)V H It comprises the amino acid sequence SEQ ID NO:103 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:103; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xxv)V H It comprises the amino acid sequence SEQ ID NO:104 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:104; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xxvi)V H It comprises the amino acid sequence SEQ ID NO:105 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:105; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xxvii)V H It comprises the amino acid sequence SEQ ID NO:106 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:106; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xxviii)V H It comprises the amino acid sequence SEQ ID NO:107 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:107; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; (xxix)V H It comprises the amino acid sequence SEQ ID NO:108 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:108; and V LIt contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; or (xxx)V H It comprises the amino acid sequence SEQ ID NO:109 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:109; and V L It contains the amino acid sequence SEQ ID NO:122 or a variant thereof, the variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122.

[0018] In some embodiments, a separate anti-C5a antibody is provided, comprising a heavy chain variable domain (V... H ), the V H It includes: a heavy chain complementarity determination region (HC-CDR)1 containing ELSMH (SEQ ID NO:3); HC-CDR2 containing GFDPX1X2GETIYAQKFQG (SEQ ID NO:72), where X1 is E or R and X2 is D or L; and HC-CDR3 containing GISX1X2WNDAFDI (SEQ ID NO:75), where X1 is D or S and X2 is G, I, or W; and a light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASQSVRNDLA (SEQ ID NO:51); LC-CDR2, which includes DASDRAT (SEQ ID NO:59); and LC-CDR3, which includes QQYMDSHPLT (SEQ ID NO:67).

[0019] In some embodiments, an isolated anti-C5a antibody is provided, which comprises V H The V H Contains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:3 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; HC-CDR2, comprising the amino acid sequence shown in any of SEQ ID NOs:32-34 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and HC-CDR3, comprising the amino acid sequence shown in any of SEQ ID NOs:38-39 and 42 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and V L The V LIt comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:51 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:59 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:67 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids.

[0020] In some embodiments, an isolated anti-C5a antibody is provided, comprising: V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:110-114 H Includes HC-CDR1, HC-CDR2, and HC-CDR3, as well as V L The V L Contains V as shown in SEQ ID NO:125 of the amino acid sequence L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0021] In some embodiments, an isolated anti-C5a antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:110. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:125. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (ii)V H It contains V as shown in the amino acid sequence SEQ ID NO:111. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:125. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iii)V H It contains V as shown in the amino acid sequence SEQ ID NO:112. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:125. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iv)V HIt contains V as shown in the amino acid sequence SEQ ID NO:113. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:125. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; or (v)V H It contains V as shown in the amino acid sequence SEQ ID NO:114. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:125. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0022] In some embodiments, an isolated anti-C5a antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:32; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:38, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51; LC-CDR2, which contains the amino acid sequence SEQ ID NO:59; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:67, or the V L (ii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:32; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V LContains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51; LC-CDR2, which contains the amino acid sequence SEQ ID NO:59; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:67, or the V L (iii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:33; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51; LC-CDR2, which contains the amino acid sequence SEQ ID NO:59; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:67, or the V L (iv) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:34; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51; LC-CDR2, which contains the amino acid sequence SEQ ID NO:59; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:67, or the V L Variants whose LC-CDRs contain substitutions of up to about 5 amino acids; or (v)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:32; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:42, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V LThe V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51; LC-CDR2, which contains the amino acid sequence SEQ ID NO:59; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:67, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0023] In some embodiments, any of the isolated anti-C5a antibodies described above, the isolated anti-C5a antibody comprising: V H It comprises any of the amino acid sequences shown in SEQ ID NOs:110-114 or variants thereof, wherein the variants have at least about 90% sequence identity with any of the amino acid sequences shown in SEQ ID NOs:110-114; and V L It contains the amino acid sequence shown in SEQ ID NO:125 or a variant thereof, the variant having at least about 90% sequence identity with the amino acid sequence shown in SEQ ID NO:125.

[0024] In some embodiments, an isolated anti-C5a antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:110 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:110; and V L It contains the amino acid sequence SEQ ID NO:125 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:125; (ii) V H It comprises the amino acid sequence SEQ ID NO:111 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:111; and V L It contains the amino acid sequence SEQ ID NO:125 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:125; (iii) V H It comprises the amino acid sequence SEQ ID NO:112 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:112; and V L It contains the amino acid sequence SEQ ID NO:125 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:125; (iv)V HIt comprises the amino acid sequence SEQ ID NO:113 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:113; and V L It comprises the amino acid sequence SEQ ID NO:125 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:125; or (v)V H It comprises the amino acid sequence SEQ ID NO:114 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:114; and V L It contains the amino acid sequence SEQ ID NO:125 or a variant thereof, the variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:125.

[0025] In some embodiments, an isolated anti-C5a antibody is provided, comprising: V H It contains V as shown in the amino acid sequence SEQ ID NO:115. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:126. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0026] In some embodiments, an isolated anti-C5a antibody is provided, comprising: V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:4; HC-CDR2, which contains the amino acid sequence SEQ ID NO:35; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:45, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:52; LC-CDR2, which contains the amino acid sequence SEQ ID NO:60; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:68, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0027] In some embodiments, any of the isolated anti-C5a antibodies described above, the isolated anti-C5a antibody comprising: V HIt comprises the amino acid sequence shown in SEQ ID NO:115 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence shown in SEQ ID NO:115; and V L It contains the amino acid sequence shown in SEQ ID NO:126 or a variant thereof, the variant having at least about 90% sequence identity with the amino acid sequence shown in SEQ ID NO:126.

[0028] In some embodiments, a separate anti-C5a antibody is provided, comprising a heavy chain variable domain (V... H ), the V H It includes: a heavy chain complementarity determination region (HC-CDR)1, which contains NYAIN (SEQ ID NO:5); HC-CDR2, which contains GIX1PFFGX2EDYAQKFQG (SEQ ID NO:73), wherein X1 is V or Y and X2 is T or W; and HC-CDR3, which contains DLLX1GFDI (SEQ ID NO:76), wherein X1 is E or H; and a light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASHDIETWLA (SEQ ID NO:53); LC-CDR2, which includes GASNLQS (SEQ ID NO:61); and LC-CDR3, which includes QQANELPYT (SEQ ID NO:69).

[0029] In some embodiments, an isolated anti-C5a antibody is provided, which comprises V H The V H Contains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:5 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; HC-CDR2, comprising the amino acid sequence shown in any of SEQ ID NOs:36-37 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and HC-CDR3, comprising the amino acid sequence shown in any of SEQ ID NOs:46-47 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and V L The V LIt comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:53 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:61 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:69 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids.

[0030] In some embodiments, an isolated anti-C5a antibody is provided, comprising: V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:116-117 H Includes HC-CDR1, HC-CDR2, and HC-CDR3, as well as V L The V L Contains V as shown in SEQ ID NO:127 of the amino acid sequence L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0031] In some embodiments, an isolated anti-C5a antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:116. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:127. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (ii)V H It contains V as shown in the amino acid sequence SEQ ID NO:117. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:127. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0032] In some embodiments, an isolated anti-C5a antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:5; HC-CDR2, which contains the amino acid sequence SEQ ID NO:36; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:46, or the V HVariants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:53; LC-CDR2, which contains the amino acid sequence SEQ ID NO:61; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:69, or the V L (ii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:5; HC-CDR2, which contains the amino acid sequence SEQ ID NO:37; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:47, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:53; LC-CDR2, which contains the amino acid sequence SEQ ID NO:61; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:69, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0033] In some embodiments, any of the isolated anti-C5a antibodies described above, the isolated anti-C5a antibody comprising: V H It comprises any of the amino acid sequences shown in SEQ ID NOs:116-117 or variants thereof, wherein the variants have at least about 90% sequence identity with any of the amino acid sequences shown in SEQ ID NOs:116-117; and V L It contains the amino acid sequence shown in SEQ ID NO:127 or a variant thereof, the variant having at least about 90% sequence identity with the amino acid sequence shown in SEQ ID NO:127.

[0034] In some embodiments, an isolated anti-C5a antibody comprises: (i) V H It comprises the amino acid sequence SEQ ID NO:116 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:116; and V L It contains the amino acid sequence SEQ ID NO:127 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:127; (ii) VH It comprises the amino acid sequence SEQ ID NO:117 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:117; and V L It contains the amino acid sequence SEQ ID NO:127 or a variant thereof, the variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:127.

[0035] In some embodiments, the Kd value of the isolated anti-C5a antibody binding to human C5a is 0.1 pM to 1 nM.

[0036] In some embodiments, an isolated anti-C5a antibody is provided that competitively binds to C5a with any of the isolated anti-C5a antibodies described above. In some embodiments, an isolated anti-C5a antibody is provided that specifically binds to the same epitope as any of the isolated anti-C5a antibodies described above.

[0037] In some embodiments, the isolated anti-C5a antibody, as described above, comprises an Fc fragment. In some embodiments, the isolated anti-C5a antibody is a full-length IgG antibody. In some embodiments, the isolated anti-C5a antibody is a full-length IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the isolated anti-C5a antibody is chimeric, fully human, or humanized. In some embodiments, the isolated anti-C5a antibody is an antigen-binding fragment selected from Fab, Fab', F(ab)'2, Fab'-SH, single-chain antibody (scFv), Fv fragment, dAb, Fd, nanobody, diabody, and linear antibody.

[0038] In some embodiments, an isolated nucleic acid molecule is provided, the nucleic acid molecule encoding any of the anti-C5a antibodies described above. In some embodiments, a vector is provided, the vector comprising any of the nucleic acid molecules described above. In some embodiments, a host cell is provided, the host cell comprising any of the anti-C5a antibodies described above, any of the nucleic acid molecules described above, or any of the vectors described above. In some embodiments, a method for preparing an anti-C5a antibody is provided, comprising: a) culturing any of the above-described host cells under conditions that enable efficient expression of the anti-C5a antibody; and b) obtaining the expressed anti-C5a antibody from the host cell.

[0039] In some embodiments, a method of treating a desired individual disease or condition is provided, comprising administering an effective amount of any of the anti-C5a antibodies described above to the individual. In some embodiments, the use of any of the anti-C5a antibodies described above in the preparation of a pharmaceutical composition for treating a desired individual disease or condition is provided. In some embodiments, the use of any of the anti-C5a antibodies described above or a pharmaceutical composition comprising an anti-C5a antibody in the preparation of a medicament for treating a disease or condition is provided. In some embodiments, the disease or condition is related to the C5a signaling pathway and includes autoimmune diseases, inflammation, cancer, pain, respiratory and / or transplant-related diseases or conditions. In some embodiments, the disease or condition is selected from, for example, SIRS, sepsis, severe sepsis, septic shock, ischemia / reperfusion-related injury, acute lung injury, pneumonia, acute and chronic transplant rejection in transplant patients, graft-versus-host disease, glomerular disease, glomerulonephritis, solid kidney failure, rheumatoid arthritis, autoimmune diseases, Bechterew's disease, lupus-like diseases, inflammatory bowel disease, Crohn's disease, tumor growth, and solid organ cancer.

[0040] It also provides pharmaceutical compositions, kits, and manufactured products containing any of the anti-C5a antibodies described above. Attached Figure Description

[0041] Figure 1A-1G The results shown are the binding affinity of an exemplary full-length anti-C5a antibody (reconstructed into human IgG4 form) to human recombinant C5a, as analyzed by ELISA.

[0042] Figure 2A-2B The results shown are the binding affinity of full-length anti-C5a antibodies H1701, H1712, 1714, H4, or H401 (reconstructed into human IgG4 form) to cynomolgus monkey C5a, as analyzed by ELISA. Figure 2C-2E The results shown are the binding affinity of an exemplary full-length anti-C5a antibody to human natural C5, as analyzed by ELISA. Figure 2C The results shown are the binding curves of full-length anti-C5a antibodies H1701, H1712, and 1714 (reconstructed into human IgG4 form) or control antibody INab308 to human natural C5. Figure 2D The results shown are the binding curves of H3 (reconstructed into human IgG4 form) or control antibody INab308 with human natural C5. Figure 2E The results shown are the binding curves of full-length anti-C5a antibody H4, H401 (reconstructed into human IgG4 form) or control antibody INab308 to human natural C5. Figure 2F-2G The results shown are the binding affinity of an exemplary full-length anti-C5a antibody to recombinant C5a-des Arg, as analyzed by ELISA.

[0043] Figure 3 The results shown are the binding specificity of optimized anti-C5a antibodies H106, H107, H108, H109, ​​H1712 or H1714 (reconstructed into human IgG4 form) to BV particles.

[0044] Figure 4A-4G The results show that, in the reactive oxygen species (ROS) release assay, the optimized full-length anti-C5a antibodies H101-H114, H1701-H1715, H201-H204, H401, and the parental C5a antibody H1-H4 (reconstructed into the human IgG4 form) inhibited ROS release.

[0045] Figure 5 The results of the calcium ion influx experiment are shown. The results indicate that the optimized full-length anti-C5a antibodies H101, H103, H104, H105, H106, H1701 or H1712 (reconstructed into human IgG4 form) can block the binding of C5a to its receptor C5aR1.

[0046] Figure 6 The results of the migration chemotaxis assay show that the optimized full-length anti-C5a antibodies H101, H103, H105, H107, H108, H1701 and H1712 (reconstructed into human IgG4 form) can significantly block C5a-induced chemotaxis and are more effective than the control antibody INab308.

[0047] Figures 7A-7B The results of the CD11b blocking experiment are shown. The results indicate that in human neutrophils, optimized anti-C5a antibodies H101, H107, H1701, H1712, and H1714 (reconstructed into human IgG4 form) can block recombinant human C5a (…). Figure 7A ) or endogenous C5a ( Figure 7B ) induces CD11b upregulation. Figure 7C The results of the CD11b blocking experiment are shown. The results indicate that the optimized anti-C5a antibodies H1702, H1703, H1706, H1710, H201, and H202 (reconstructed into human IgG4 form) comprehensively block C5a activity in a dose-dependent manner.

[0048] Figures 8A-8D The results shown represent the plasma hemolytic activity of anti-C5a antibodies. In the classical activation pathway, compared to the control antibody Eculizumab, anti-C5a antibodies H106, H108, H111, H112, H113, and H114 (reconstructed into adult IgG4 form) (…). Figure 8AOr anti-C5a antibodies H1701, H1712, H1714, H4, H401 (reconstructed into adult IgG4 form) Figure 8B ) does not inhibit plasma hemolytic activity. In the bypass activation pathway, compared with the control antibody Eculizumab, anti-C5a antibodies H101, H103, H105, H1701, and H1702 (reconstructed into adult IgG4 form) ( Figure 8C Or anti-C5a antibodies H106, H107, H108, H109, ​​H110, H111, H112, H113, H114, H1701, H1706, H1710, H1712, H1714 (reconstructed into adult IgG4 form) Figure 8D It does not inhibit plasma hemolytic activity.

[0049] Figure 9 The results shown demonstrate the inhibitory effect of optimized anti-C5a antibodies H101 or H1712 (reconstructed into human IgG4 form) on C5a-induced mouse neutrophil chemotaxis.

[0050] Figures 10A-10B The results shown are the pharmacokinetic analysis results in rats. Measurements were taken by ELISA after subcutaneous injection (…). Figure 10A ) or intravenous injection ( Figure 10B The half-life of anti-C5a antibodies H1701, H1712, and H1714 (reconstructed into human IgG4 form) in rats.

[0051] Detailed description of this application

[0052] This invention relates, in one aspect, to anti-C5a antibody molecules. Through a combination of screening a natural scFv phage library, affinity maturation, and appropriately designed biochemical and biological experiments, we have identified highly efficient antibody molecules capable of binding to and inhibiting the activity of human C5a. In some embodiments, the isolated anti-C5a antibody or antigen-binding fragment binds both human C5 and C5a. C5a is known to be an essential component in the pathogenesis of complement-related disorders, including but not limited to sepsis, rheumatoid arthritis, and asthma. Since the concentration of C5 in human serum is much higher than that of C5a, high concentrations and / or frequent administration of anti-C5a antibodies would be required if antibodies were to bind to C5 and C5a with equal binding capacity. The advantage of the antibody or antigen-binding fragment described herein is that our antibody binds to C5a with an affinity comparable to or better than the control antibody INab308, while binding to C5 with a lower affinity than INab308, and surprisingly, our antibody has demonstrated even greater efficacy than INab308 in various biological experiments.

[0053] The anti-C5a antibodies provided in this application include, for example, full-length anti-C5a antibodies, anti-C5a single-chain antibodies (scFvs), anti-C5a Fc fusion proteins, multispecific (e.g., bispecific) anti-C5a antibodies, anti-C5a immunoconjugates, and the like.

[0054] On the other hand, this application provides an anti-C5a antibody, wherein the anti-C5a antibody comprises a heavy chain variable domain (V H ), the V H It includes: a heavy chain complementarity determination region (HC-CDR)1, which contains X1LSX2H (SEQ ID NO:70), wherein X1 is D or E, and X2 is I or M; HC-CDR2, which contains GFX1PX2X3GX4TIYAQNFQG (SEQ ID NO:71), wherein X1 is A, D, E, G, L, N, P, Q, S, V or Y, X2 is D, E, F, I, L, N, R, S, T or V, X3 is A, D, F, I, L, N, Q or S, and X4 is D, G, T or V; and HC-CDR3, which contains GISX1X2X3NDAFDI (SEQ ID NO:74), wherein X1 is D, E or S, X2 is A, G, I, V or W, and X3 is H or W; and a light chain variable structural domain (V L ), the V L It includes: a light chain complementarity determination region (LC-CDR)1, which includes RASQSVX1SX2YLA (SEQ ID NO: 77), wherein X1 is K or S and X2 is N, R or S; LC-CDR2, which includes DASX1RX2T (SEQ ID NO: 78), wherein X1 is A, D, E or S and X2 is A, D or S; and LC-CDR3, which includes QQYYX1X2PX3T (SEQ ID NO: 79), wherein X1 is A, D or I, X2 is L, P or S and X3 is I, L or T.

[0055] On the other hand, this application provides an anti-C5a antibody, wherein the anti-C5a antibody comprises a heavy chain variable domain (V H ), the V H It includes: a heavy chain complementarity determination region (HC-CDR)1 containing ELSMH (SEQ ID NO:3); HC-CDR2 containing GFDPX1X2GETIYAQKFQG (SEQ ID NO:72), where X1 is E or R and X2 is D or L; and HC-CDR3 containing GISX1X2WNDAFDI (SEQ ID NO:75), where X1 is D or S and X2 is G, I, or W; and a light chain variable structural domain (V L ), the V LIt includes: light chain complementarity determination region (LC-CDR)1, which includes RASQSVRNDLA (SEQ ID NO:51); LC-CDR2, which includes DASDRAT (SEQ ID NO:59); and LC-CDR3, which includes QQYMDSHPLT (SEQ ID NO:67).

[0056] On the other hand, this application provides an anti-C5a antibody, wherein the anti-C5a antibody comprises: a heavy chain variable domain (V H ), the V H It includes: a heavy chain complementarity-determining region (HC-CDR)1 containing SYWIG (SEQ ID NO:4); HC-CDR2 containing IIYPGDSDTRYSPSFQG (SEQ ID NO:35); and HC-CDR3 containing RAYGPVSSVAFDI (SEQ ID NO:45); and a light chain variable domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASQGIRNDLG (SEQ ID NO:52); LC-CDR2, which includes AASSLQS (SEQ ID NO:60); and LC-CDR3, which includes LQDYSYPLT (SEQ ID NO:68).

[0057] On the other hand, this application provides an anti-C5a antibody, wherein the anti-C5a antibody comprises a heavy chain variable domain (V H ), the V H It includes: a heavy chain complementarity determination region (HC-CDR)1, which contains NYAIN (SEQ ID NO:5); HC-CDR2, which contains GIX1PFFGX2EDYAQKFQG (SEQ ID NO:73), wherein X1 is V or Y and X2 is T or W; and HC-CDR3, which contains DLLX1GFDI (SEQ ID NO:76), wherein X1 is E or H; and a light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASHDIETWLA (SEQ ID NO:53); LC-CDR2, which includes GASNLQS (SEQ ID NO:61); and LC-CDR3, which includes QQANELPYT (SEQ ID NO:69).

[0058] It also provides nucleic acids encoding anti-C5a antibodies, compositions containing anti-C5a antibodies, and methods for preparing and using anti-C5a antibodies.

[0059] definition

[0060] As described herein, “treatment” or “treating” is a method of obtaining a beneficial or desired outcome, including clinical outcomes. For the purposes of this application, the beneficial or desired clinical outcome includes, but is not limited to, one or more of the following: relief of one or more symptoms caused by a disease, reduction of disease severity, stabilization of the disease (e.g., prevention or delay of disease exacerbation), prevention or delay of disease spread (e.g., metastasis), prevention or delay of disease recurrence, delay or slowing of disease progression, improvement of disease status, relief of the disease (partial or complete), reduction of the dosage of one or more other medications required to treat the disease, delay of disease progression, improvement or enhancement of quality of life, weight gain, and / or prolonged survival. Simultaneously, “treatment” also includes a reduction in disease pathological outcomes (e.g., tumor volume in the case of cancer). The methods of this application consider any one or more aspects of these treatments.

[0061] The term "antibody" includes both full-length antibodies and their antigen-binding fragments. Full-length antibodies consist of two heavy chains and two light chains. Variable regions in both the light and heavy chains are responsible for antigen binding. The variable regions in both chains typically include three hypervariable loops, referred to as complementarity-determining regions (CDRs) (light chain (LC) CDRs include LC-CDR1, LC-CDR2, and LC-CDR3; heavy chain (HC) CDRs include HC-CDR1, HC-CDR2, and HC-CDR3). The CDR boundaries of the antibodies or antigen-binding fragments disclosed herein can be defined or identified according to the Kabat, Chothia, or Al-Lazikani conventions (Al-Lazikani 1997; Chothia 1985; Chothia 1987; Chothia 1989; Kabat 1987; Kabat 1991). Three CDR regions of the heavy or light chain are inserted between flanking segments called framework regions (FRs), which are more conserved than the CDR regions and form a scaffold supporting the hypervariable loop. The constant regions of the heavy and light chains do not participate in antigen binding but exhibit a variety of effector functions. Antibodies are classified based on the amino acid sequence of their heavy chain constant regions. The five main classes or isotypes of antibodies are IgA, IgD, IgE, IgG, and IgM, characterized by having α, δ, ε, γ, and μ-type heavy chains, respectively. Several major antibody classes are subclassed, such as IgG1 (γ1 heavy chain), IgG2 (γ2 heavy chain), IgG3 (γ3 heavy chain), IgG4 (γ4 heavy chain), IgA1 (α1 heavy chain), or IgA2 (α2 heavy chain).

[0062] As described herein, the term "antigen-binding fragment" includes antibody fragments such as diabody, Fab, Fab', F(ab')2, Fv fragment, disulfide-stabilized Fv fragment (dsFv), (dsFv)2, bispecific dsFv (dsFv-dsFv'), disulfide-stabilized diabody (ds-diabody), single-chain antibody (scFv), scFv dimer (bivalent diabody), multispecific antibody, single-domain antibody, nanobody, domain antibody, divalent domain antibody, or any other antibody fragment capable of binding to an antigen but not containing a complete antibody structure. An antigen-binding fragment is capable of binding the same antigen to a parent antibody or a parent antibody fragment (such as a parental scFv). In some embodiments, an antigen-binding fragment may include one or more CDRs from a specific human antibody that have been grafted into a frame region from one or more different human antibodies.

[0063] As described herein, the term "epitope" refers to a specific set of atoms or amino acids on an antigen that an antibody or antibody portion binds to. If two antibodies or antibody portions exhibit competitive binding to an antigen, they may bind to the same epitope on the antigen.

[0064] As used herein, when the first antibody inhibits the binding of the second antibody to the C5a target by at least 50% (e.g., at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%) at an equimolar concentration, the first antibody “competitively” binds to the C5a target with the second antibody, and vice versa. PCT Publication WO 03 / 48731 describes a high-throughput antibody “epitope classification” method based on cross-competition.

[0065] As described herein, the terms "specifically bind," "specifically recognize," or "specific to" refer to measurable and reproducible interactions, such as antibody binding to a target that confirms the presence of that target in a heterogeneous group of molecules, including biomolecules. For example, an antibody's ability to specifically recognize a target (which may be an epitope) means that the antibody binds to that target with higher affinity, stronger binding, and / or more persistent binding compared to binding to other targets. In some embodiments, an antibody that specifically recognizes an antigen reacts with one or more antigenic determinants of the antigen with a binding affinity at least 10 times greater than its binding affinity to other targets.

[0066] As described herein, an “isolated” anti-C5a antibody is an anti-C5a antibody that (1) is not related to a naturally occurring protein, (2) does not contain other proteins of the same origin, (3) is expressed by cells of a different species, or (4) does not exist in nature.

[0067] As described herein, the term “isolated nucleic acid” refers to a nucleic acid or combination thereof of genomic, cDNA, or synthetic origin. Depending on its origin, “isolated nucleic acid” means that it is (1) unrelated to all or part of the polynucleotides in “isolated nucleic acids” found in nature, (2) operablely ligable to polynucleotides not naturally associated with it, or (3) not present in nature as part of a longer sequence.

[0068] As used herein, the term “CDR” or “complementarity-determining region” refers to a discontinuous antigen-binding site found within the variable domains of heavy and light chain polypeptides. In the literature Kabat et al., J. Biol. Chem. 252: 6609-6616 (1977); Kabat et al., USDept. of Health and Human Services, "Sequences of proteins of immunological interest" (1991); Chothia et al., J. Mol. Biol. 196: 901-917 (1987); Al-Lazikani B. et al. al., J. Mol. Biol., 273: 927-948 (1997); MacCallum et al., J. Mol. Biol. 262: 732-745 (1996); Abhinandan and Martin, Mol. Immunol., 45: 3832-3839 (2008); Lefranc MPet These specific regions have been described in al., Dev. Comp. Immunol., 27:55-77 (2003); and Honegger and Plückthun, J. Mol. Biol., 309:657-670 (2001), where these definitions include overlaps or subsets of amino acid residues when compared with each other. However, any definition used to indicate a CDR of an antibody or transplanted antibody or its variants is included within the scope of the terminology defined and used herein. Table 1 lists the positions of the amino acid residues included in the CDRs defined by the aforementioned references for comparison. Algorithms and interfaces for CDR prediction are known in the art, including, for example, those described in Abhinandan and Martin, Mol. Immunol., 45:3832-3839 (2008); Ehrenmann F. et al., Nucleic Acids Res., 38:D301-D307 (2010); and Adolf-Bryfogle J. et al., Nucleic Acids Res., 43:D432-D438 (2015). The entire contents of the references cited in this paragraph are incorporated herein by reference for the purposes of this application and one or more claims that may be included herein.

[0069] Table 1: CDR Definition

[0070] <![CDATA[Kabat 1 ]]> <![CDATA[Chothia 2 ]]> <![CDATA[MacCallum 3 ]]> <![CDATA[IMGT 4 ]]> <![CDATA[AHo 5 ]]> <![CDATA[V H CDR1]]> 31-35 26-32 30-35 27-38 25-40 <![CDATA[V H CDR2]]> 50-65 53-55 47-58 56-65 58-77 <![CDATA[V H CDR3]]> 95-102 96-101 93-101 105-117 109-137 <![CDATA[V L CDR1]]> 24-34 26-32 30-36 27-38 25-40 <![CDATA[V L CDR2]]> 50-56 50-52 46-55 56-65 58-77 <![CDATA[V L CDR3]]> 89-97 91-96 89-96 105-117 109-137

[0071] 1 The amino acid residue numbering follows the nomenclature method described in Kabat et al. above.

[0072] 2 The amino acid residue numbering follows the nomenclature method described in Chothia et al. above.

[0073] 3 The amino acid residue numbering follows the nomenclature method described in MacCallum et al. above.

[0074] 4 The amino acid residue numbering follows the nomenclature method described in Lefranc et al. above.

[0075] 5 The amino acid residue numbering follows the nomenclature method described in Honegger and Plückthun.

[0076] The term "chimeric antibody" refers to an antibody in which a portion of the heavy chain and / or light chain is identical or homologous to the corresponding sequence in an antibody from a particular species or belonging to a particular antibody species or subclass, while the remainder of the chain is identical or homologous to the corresponding sequence in an antibody from another genus or belonging to another antibody species or subclass, as well as fragments of such antibodies, provided they possess the biological activity described in this application (see US Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)).

[0077] "Fv" is the smallest antibody fragment containing a complete antigen recognition and binding site. This fragment is a dimer formed by a heavy chain variable domain and a light chain variable domain tightly and non-covalently linked. The folding of these two domains derives six hypervariable rings (three in the light chain and three in the heavy chain), which provide the antibody with amino acid residues for binding to the antigen and confer the antibody's specificity for antigen binding. However, even a single variable domain (or half of the Fv fragment, containing only three antigen-specific CDRs) can recognize and bind to antigens, although its affinity is lower than that of the complete binding site.

[0078] "Single-chain Fv", also abbreviated as "sFv" or "scFv", is a type of Fv containing V molecules linked together to form a single polypeptide chain. H and V L Antibody fragments of antibody domains. In some embodiments, the scFv polypeptide further includes V H and V LThe linker polypeptide between the domains allows scFv to form an ideal structure for antigen binding. For an overview of scFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994).

[0079] The term "diabodies" is used in V H and V L Small antibody fragments are prepared by constructing scFv fragments (see above) using short linkers (e.g., 5–10 residues) between domains. This allows the variable domains to pair between chains rather than within chains, resulting in a bivalent fragment, i.e., a fragment with two antigen-binding sites. Bispecific double-chain antibodies are heterodimers of two “crossed” scFv fragments, where the V0 of the two antibodies... H and V L The domains are located on different polypeptide chains. Double-chain antibodies are fully described in EP 404,097; WO93 / 11161; Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).

[0080] The “humanized” form of non-human (e.g., rodent) antibodies is a chimeric antibody, which includes a minimal sequence derived from the non-human antibody. In most cases, humanized antibodies are human immunoglobulins (receptor antibodies), where the hypervariable region (HVR) residues of the receptor antibody are replaced by hypervariable region residues from non-human species such as mice, rats, rabbits, or non-human mammals that possess desirable antibody specificity, affinity, and performance (donor antibody). In some cases, residues in the human immunoglobulin framework region are replaced by corresponding non-human residues. Additionally, humanized antibodies may include residues not present in either the receptor or donor antibody. These modifications can further improve antibody performance. Typically, humanized antibodies contain substantially all, at least one, and usually two variable domains, where all or substantially all of the hypervariable loops correspond to the hypervariable loops of a non-human immunoglobulin, and all or substantially all of the framework regions are human immunoglobulin sequences. Humanized antibodies may also optionally include at least a portion of the immunoglobulin constant region (Fc), typically the constant region of a human immunoglobulin. For details, please refer to Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992).

[0081] The "percentage of amino acid sequence identity (%)" or "homology" of the peptide and antibody sequences identified in this paper is defined as the percentage of identical amino acid residues in a candidate sequence compared to a peptide sequence, assuming that conserved substitutions are part of sequence identity. The percentage of amino acid sequence identity can be determined using various alignment methods within the scope of the art, such as publicly available computer software like BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), or MUSCLE software. Those skilled in the art can determine suitable parameters for measuring alignment, including any algorithm required to maximize alignment across the full length of the compared sequences. However, for the purposes of this paper, the percentage of amino acid sequence identity values ​​were generated using the sequence alignment computer program MUSCLE (Edgar, RC, Nucleic Acids Research 32(5):1792-1797, 2004; Edgar, RC, BMC Bioinformatics 5(1):113, 2004).

[0082] The term "Fc receptor" or "FcR" is used to describe receptors that bind to the Fc region of antibodies. In some embodiments, the FcR described in this application is an FcR that binds to IgG antibodies (a type of γ receptor), including receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternative splicing forms of these receptors. FcγRII receptors include FcγRIIA ("activating receptor") and FcγRIIB ("inhibiting receptor"), which have similar amino acid sequences and differ primarily in their cytoplasmic domains. The cytoplasmic domain of the activating receptor FcγRIIA contains an immunoreceptor tyrosine activation motif (ITAM). The cytoplasmic domain of the inhibitory receptor FcγRIIB contains an immunoreceptor tyrosine inhibitory motif (ITIM) (see M.in.). Annu.Rev.Immunol.15:203-234 (1997)). The term also includes allotypes, such as FcγRIIIA allotypes: FcγRIIIA-Phe158, FcγRIIIA-Val158, FcγRIIA-R131 and / or FcγRIIA-H131. FcRs are described in Ravetch and Kinet, Annu.Rev.Immunol 9:457-92 (1991) and Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J.Lab.Clin.Med.126:330-41 (1995). In this application, the term FcR covers other types of FcRs, including those to be identified in the future. The term FcR also includes the neonatal receptor FcRn, which is responsible for transferring maternal IgGs to the newborn (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994)).

[0083] The term "FcRn" refers to the neonatal Fc receptor (FcRn). FcRn is structurally similar to the major histocompatibility complex (MHC), consisting of an α-chain non-covalently bound to β2-microglobulin. The various functions of the neonatal Fc receptor FcRn are reviewed in Ghetie and Ward (2000) Annu. Rev. Immunol. 18, 739-766. FcRn plays an important role in the passive transport of immunoglobulin IgGs from the mother to the newborn and in regulating serum IgG levels. As a rescue receptor, FcRn can bind and transport endocytotic IgG in its intact form both intracellularly and intercellularly, protecting it from the default degradation pathway.

[0084] The "CH1 domain" of the human IgG Fc region typically extends from amino acid 118 to amino acid 215 (EU numbering system).

[0085] The "hinge region" is typically defined as extending from Glu at position 216 to Pro at position 230 of human IgG1 (Burton, Molec. Immunol. 22:161-206 (1985)). By placing the first and last cysteine ​​residues that form the inter-heavy chain disulfide bond at the same positions as IgG1, it is possible to align the hinge regions of other IgG isotypes with the IgG1 sequence.

[0086] The "CH2 domain" of the human IgG Fc region typically extends from amino acid 231 to amino acid 340. The unique feature of the CH2 domain is that it does not pair tightly with another region; instead, two N-terminal branched sugar chains are inserted between the two CH2 domains of the intact native IgG molecule. It is speculated that the sugars may act as a substitute for domain-to-domain pairing, helping to maintain the stability of the CH2 domain. (Burton, Molec. Immunol. 22:161-206 (1985)).

[0087] The “CH3” domain includes the extension from the C-terminal residue to the CH2 domain within the Fc region (from amino acid 341 to the C-terminus of the antibody sequence, typically amino acid 446 or 447 of IgG).

[0088] "Functional Fc fragments" possess the "effective functions" inherent in the natural Fc region sequence. Exemplary "effective functions" include C1q binding; complement-dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; and downregulation of cell surface receptors (such as B cell receptors; BCR). These effector functions typically require the Fc region to bind to a binding domain (such as the antibody variable region) and can be evaluated using a variety of experimental methods known in the art.

[0089] Antibodies with IgG Fc variants exhibiting "altered" FcR binding affinity or ADCC activity show enhanced or weakened FcR binding and / or ADCC activity compared to the parent peptide or peptides containing the native Fc sequence. Fc variants exhibiting "enhanced binding" to FcRs have higher binding affinity (e.g., lower apparent Kd or IC50) to at least one FcR compared to the parent peptide or peptides containing the native IgG Fc sequence. 50(Value). In some embodiments, the binding affinity is enhanced by 3 times compared to the parent peptide, for example, 5, 10, 25, 50, 60, 100, 150, 200, or even up to 500 times, or the binding affinity is increased by 25% to 1000%. Fc variants exhibit “reduced binding” to FcRs, having a lower affinity for at least one FcR compared to the parent peptide (e.g., higher apparent Kd or IC). 50 (Value). Compared with the parent peptide, its binding ability is reduced by 40% or more.

[0090] Antibody-dependent cell-mediated cytotoxicity (ADCC) is a form of cytotoxicity in which secreted Ig binds to Fc receptors (FcRs) present on certain cytotoxic cells (e.g., natural killer (NK) cells, neutrophils, and macrophages). This allows these cytotoxic effector cells to specifically bind to target cells carrying antigens and subsequently kill the target cells using cytotoxins. Antibodies "arm" the cytotoxic cells and are essential for this killing. Among the main cell types mediating ADCC, NK cells express only FcγRIII, while monocytes express FcγRI, FcγRII, and FcγRIII. The expression of FcRs on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991). The ADCC activity of target molecules can be assessed by in vitro ADCC experiments, described in U.S. Patent Nos. 5,500,362 or 5,821,337. Effector cells suitable for such experiments include peripheral blood mononuclear cells (PBMCs) and natural killer cells (NK cells). Alternatively, or additionally, the ADCC activity of the target molecule can also be assessed in vivo, as described, for example, in animal models disclosed in Clynes et al. PNAS (USA) 95:652-656 (1998).

[0091] Peptides containing Fc region variants exhibit "enhanced ADCC activity" or are more effective at mediating ADCC effects in the presence of human effector cells compared to peptides containing wild-type IgG Fc or parental peptides. These peptides, when experimentally present in substantially the same quantity as those containing wild-type IgG Fc (or parental peptides), mediate ADCC more effectively both in vitro and in vivo. Such variants are typically identified using any in vitro ADCC assay known in the art, such as experiments or methods for identifying ADCC activity, for example in animal models. In some embodiments, such variants mediate ADCC with a 5 to 100-fold, for example, 25 to 50-fold, efficiency improvement compared to wild-type Fc (or parental peptide).

[0092] "Complement-dependent cytotoxicity" or "CDC" refers to the lysis of target cells in the presence of complement. Activation of the classical complement pathway is initiated by the binding of the first component of the complement system (C1q) to an antibody (a subclass with a suitable structure) that binds to a homologous antigen. To assess complement activation, CDC assays can be performed, as described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996). Peptide variants with altered Fc region amino acid sequences and increased or decreased C1q binding capacity are described in U.S. Patent Nos. 6,194,551B1 and WO99 / 51642. The contents of these patent publications are expressly incorporated herein by reference. See also Idusogie et al. J. Immunol. 164:4178-4184 (2000).

[0093] Unless otherwise stated, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate forms of each other and encode the same amino acid sequence. Nucleotide sequences encoding proteins or RNA may also include introns; for example, nucleotide sequences encoding proteins may contain introns in certain forms.

[0094] The term "operationally ligated" refers to a functional link between a regulatory sequence and a heterologous nucleotide sequence, thereby enabling the latter to be expressed. For example, the first and second nucleotide sequences are operably ligated when they are in a functional relationship. Similarly, if a promoter affects the transcription or expression of a coding sequence, the promoter and coding sequence are operably ligated. Typically, operably ligated DNA sequences are contiguous, and, if necessary, two protein-coding regions can be ligated within the same reading frame.

[0095] "Homology" refers to the sequence similarity or identity between two polypeptides or two nucleic acid molecules. If the same position in two compared sequences is the same base or amino acid monomer subunit, for example, if both DNA molecules have adenine at the same position, then the two DNA molecules are homologous at that position. The percentage of homology between two sequences is a function calculated by multiplying the number of matching or homologous positions in the two sequences to the total number of positions, and then multiplying by 100. For example, if 6 out of 10 positions in two sequences are matching or homologous, then the two sequences are 60% homologous. For instance, the DNA sequences ATTGCC and TATGGC have 50% homology. Generally, when comparing two sequences, the goal is to obtain the maximum homology.

[0096] The “effective amount” of the anti-C5a antibody or composition disclosed herein refers to an amount sufficient to achieve a specific purpose. The “effective amount” can be determined empirically and by known methods associated with the stated purpose.

[0097] The term "therapeutic effective amount" refers to the dosage at which the anti-C5a antibody or its composition disclosed herein can effectively treat an individual's disease or symptoms. For example, in the case of cancer, a therapeutic effective amount of the anti-C5a antibody or its composition means the ability to reduce the number of cancer cells; reduce the size or weight of the tumor; inhibit (i.e., to some extent slow down or preferably stop) the invasion of tumor cells into surrounding organs; inhibit (i.e., to some extent slow down or preferably stop) tumor metastasis; inhibit tumor growth to some extent; and / or alleviate one or more cancer-related symptoms to some extent. The anti-C5a antibody or its composition disclosed herein can, to some extent, prevent and / or kill existing tumor cells; this can be cytoseptic or cytotoxic. In some embodiments, a therapeutic effective amount means the dosage at which the patient's survival is prolonged. In some embodiments, a therapeutic effective amount means the dosage at which the patient's progression-free survival is improved.

[0098] As used herein, "pharmaceuticalally acceptable" or "pharmacologically compatible" means a material that has no biological activity or other undesirable properties, such as the ability to be incorporated into a pharmaceutical composition given to a patient without causing significant adverse biological reactions, or that does not interact harmfully with any other components contained in the composition. Pharmaceutically acceptable carriers or excipients preferably meet the required standards for toxicological or manufacturing testing and / or are included in the inactive ingredient guidelines prepared by the U.S. Food and Drug Administration.

[0099] The embodiments of this application described herein should be understood to include embodiments that are “composed of” and / or “substantially composed of”.

[0100] In this article, “about” is used to refer to a numerical value or parameter, including (and descriptions) variations for that value or parameter itself. For example, a description involving “about X” includes a description of “X”.

[0101] As used in this article, mentioning "not" a value or parameter usually means and describes something other than a certain value or parameter. For example, "This method cannot be used to treat type X cancer" means that this method is generally used to treat other types of cancer besides type X cancer.

[0102] Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the” used herein and in the claims include plural objects.

[0103] anti-C5a antibody

[0104] On one hand, this application provides anti-C5a antibodies that specifically bind to C5a. These anti-C5a antibodies include, but are not limited to, humanized antibodies, chimeric antibodies, mouse antibodies, human antibodies, and antibody molecules comprising heavy chain and / or light chain CDRs as described herein. On the other hand, this application provides isolated antibodies that bind to C5a. Anticipated anti-C5a antibodies include, for example, full-length anti-C5a antibodies (such as full-length IgG1 or IgG4), anti-C5a single-chain antibodies, anti-C5a Fc fusion proteins, multispecific (such as bispecific) anti-C5a antibodies, anti-C5a immunoconjugates, and the like. In some embodiments, the anti-C5a antibody is a full-length antibody (such as full-length IgG1 or IgG4) or its antigen-binding fragment that specifically binds to C5a. In some embodiments, the anti-C5a antibody is Fab, Fab', F(ab)'2, Fab'-SH, single-chain antibody (scFv), Fv fragment, dAb, Fd, nanobody, diabody, or linear antibody. In some embodiments, an antibody that specifically binds to C5a means that the antibody's affinity for binding to C5a is at least 10 times greater than its affinity for binding to non-target antibodies (including, for example, 10, 10). 2 10 3 10 4 10 5 10 6 , or 10 7 (Multiple times). In some embodiments, non-target refers to an antigen that is not C5a. Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence-activated cell sorting (FACS) analysis, or radioimmunoprecipitation (RIA). Kd value can be determined by methods known in the art, such as surface plasmon resonance (SPR) technology or biolayer interference (BLI) technology.

[0105] While this document discusses anti-C5a antibodies containing human sequences (e.g., human heavy and light chain variable domains containing human CDR sequences), non-human anti-C5a antibodies are also considered. In some embodiments, a non-human anti-C5a antibody comprises the human CDR sequence and non-human frame region sequence of the anti-C5a antibody described herein. In some embodiments, the non-human frame region sequence comprises any sequence used to generate heavy and / or light chain variable domains using one or more human CDR sequences as described herein, including, for example, mammals such as mice, rats, rabbits, pigs, cattle (e.g., bulls, buffalo), deer, sheep, goats, chickens, cats, dogs, ferrets, primates (e.g., apes, macaques), etc. In some embodiments, a non-human anti-C5a antibody comprises an anti-C5a antibody generated by transplanting one or more human CDR sequences as described herein into a non-human frame region (e.g., a mouse or chicken frame region sequence).

[0106] The complete amino acid sequence of the exemplary human C5a contains or consists of the amino acid sequence shown in SEQ ID NO: 132.

[0107] In some embodiments, the anti-C5a antibody described herein specifically recognizes an epitope in human C5a. In some embodiments, the anti-C5a antibody cross-reacts with C5a from species other than humans. In some embodiments, the anti-C5a antibody is completely specific to human C5a and does not cross-react with other non-human species.

[0108] In some embodiments, the anti-C5a antibody cross-reacts with at least one allelic variant of the C5a protein (or a fragment thereof). In some embodiments, the allelic variant has up to 30 amino acid substitutions (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30) compared to the naturally occurring C5a protein (or a fragment thereof) (e.g., conserved substitutions). In some embodiments, the anti-C5a antibody does not cross-react with any allelic variant of the C5a protein (or a fragment thereof).

[0109] In some embodiments, the anti-C5a antibody cross-reacts with at least one interspecies variant of the C5a protein. In some embodiments, for example, the C5a protein (or a fragment thereof) is human C5a, and the interspecies variant of the C5a protein (or a fragment thereof) is a variant found in cynomolgus monkeys. In some embodiments, the anti-C5a antibody does not cross-react with any interspecies variant of the C5a protein.

[0110] In some embodiments, any anti-C5a antibody as described herein includes an antibody heavy chain constant region and an antibody light chain constant region. In some embodiments, the anti-C5a antibody includes an IgG1 type heavy chain constant region. In some embodiments, the anti-C5a antibody includes an IgG2 type heavy chain constant region. In some embodiments, the anti-C5a antibody includes an IgG3 type heavy chain constant region. In some embodiments, the anti-C5a antibody includes an IgG4 type heavy chain constant region. In some embodiments, the heavy chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:128. In some embodiments, the heavy chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:129. In some embodiments, the anti-C5a antibody includes a κ light chain constant region. In some embodiments, the light chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:130. In some embodiments, the anti-C5a antibody includes a λ light chain constant region. In some embodiments, the light chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:131. In some embodiments, the anti-C5a antibody includes a variable domain of the antibody heavy chain and a variable domain of the antibody light chain.

[0111] In some embodiments, the anti-C5a antibody includes a heavy chain variable domain (V... H ), the V H It includes: a heavy chain complementarity determination region (HC-CDR)1, which contains X1LSX2H (SEQ ID NO:70), wherein X1 is D or E, and X2 is I or M; HC-CDR2, which contains GFX1PX2X3GX4TIYAQNFQG (SEQ ID NO:71), wherein X1 is A, D, E, G, L, N, P, Q, S, V or Y, X2 is D, E, F, I, L, N, R, S, T or V, X3 is A, D, F, I, L, N, Q or S, and X4 is D, G, T or V; and HC-CDR3, which contains GISX1X2X3NDAFDI (SEQ ID NO:74), wherein X1 is D, E or S, X2 is A, G, I, V or W, and X3 is H or W; and a light chain variable structural domain (V L ), the V LIt includes: a light chain complementarity determination region (LC-CDR)1, which includes RASQSVX1SX2YLA (SEQ ID NO: 77), wherein X1 is K or S and X2 is N, R or S; LC-CDR2, which includes DASX1RX2T (SEQ ID NO: 78), wherein X1 is A, D, E or S and X2 is A, D or S; and LC-CDR3, which includes QQYYX1X2PX3T (SEQ ID NO: 79), wherein X1 is A, D or I, X2 is L, P or S and X3 is I, L or T.

[0112] In some embodiments, the anti-C5a antibody comprises V H The V H It comprises: HC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:1-3 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; HC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:6-31 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and HC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:38-44 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0113] In some embodiments, the anti-C5a antibody comprises V H The V H It comprises: HC-CDR1, which contains any of the amino acid sequences shown in SEQ ID NOs:1-3; HC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:6-31; and HC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:38-44.

[0114] In some embodiments, the anti-C5a antibody comprises V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:48-50 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:54-58 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:62-66 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0115] In some embodiments, the anti-C5a antibody comprises V L The V L It includes: LC-CDR1, which contains any of the amino acid sequences shown in SEQ ID NOs:48-50; LC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:54-58; and LC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:62-66.

[0116] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-3 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:6-31 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:38-44 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:48-50 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:54-58 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:62-66 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0117] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains any of the amino acid sequences shown in SEQ ID NOs:1-3; HC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:6-31; and HC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:38-44; and V L The V LIt comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:48-50; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:54-58; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:62-66.

[0118] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:6; HC-CDR3, which contains the amino acid sequence SEQ ID NO:38; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; LC-CDR3, which contains the amino acid sequence SEQ ID NO:62; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0119] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:6; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:38; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:62.

[0120] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:6; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; LC-CDR3, which contains the amino acid sequence SEQ ID NO:62; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0121] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:6; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:62.

[0122] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:7; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; LC-CDR3, which contains the amino acid sequence SEQ ID NO:62; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0123] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:7; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:62.

[0124] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; HC-CDR3, which contains the amino acid sequence SEQ ID NO:40; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; LC-CDR3, which contains the amino acid sequence SEQ ID NO:63; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0125] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:40; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:63.

[0126] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:9; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; LC-CDR3, which contains the amino acid sequence SEQ ID NO:64; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0127] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:9; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:64.

[0128] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; HC-CDR3, which contains the amino acid sequence SEQ ID NO:41; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; LC-CDR3, which contains the amino acid sequence SEQ ID NO:62; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0129] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:41; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:62.

[0130] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:11; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:55; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0131] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:11; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:55; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0132] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0133] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0134] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:13; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:49; LC-CDR2, which contains the amino acid sequence SEQ ID NO:57; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0135] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:13; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:49, LC-CDR2, which contains the amino acid sequence SEQ ID NO:57, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0136] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:14; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:50; LC-CDR2, which contains the amino acid sequence SEQ ID NO:58; LC-CDR3, which contains the amino acid sequence SEQ ID NO:66; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0137] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:14; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:50, LC-CDR2, which contains the amino acid sequence SEQ ID NO:58, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:66.

[0138] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:15; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0139] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:15; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0140] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:16; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0141] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:16; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0142] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:17; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0143] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:17; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0144] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:18; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0145] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:18; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0146] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:19; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0147] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:19; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0148] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; HC-CDR3, which contains the amino acid sequence SEQ ID NO:42; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0149] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:42; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0150] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; HC-CDR3, which contains the amino acid sequence SEQ ID NO:43; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0151] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:43; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0152] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; HC-CDR3, which contains the amino acid sequence SEQ ID NO:44; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0153] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:44; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0154] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:20; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0155] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:20; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0156] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:21; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0157] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:21; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0158] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:22; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0159] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:22; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0160] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:23; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0161] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:23; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0162] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:24; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0163] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:24; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0164] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:25; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0165] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:25; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0166] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:26; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0167] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:26; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0168] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:27; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0169] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:27; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0170] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:28; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0171] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:28; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0172] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:29; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0173] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:29; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0174] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:30; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0175] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:30; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0176] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:31; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; LC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0177] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:31; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:48; LC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:65.

[0178] In some embodiments, the anti-C5a antibody includes V H The V H Contains any amino acid sequence from SEQ ID NOs:1-3, 6-31, 38-44 or a variant thereof, said variant containing substitutions of up to about 5 amino acids; and V L The V L Containing any amino acid sequence or a variant thereof from SEQ ID NOs:48-50, 54-58, 62-66, wherein the variant contains substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody comprises: V H The V H Contains any amino acid sequence from SEQ ID NOs:1-3, 6-31, 38-44; and V L The V L It contains any of the amino acid sequences in SEQ ID NOs:48-50, 54-58, and 62-66.

[0179] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:1, 6, and 38, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 54, and 62, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:1, 6, and 38; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 54 and 62.

[0180] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 6, and 39, or the V HVariants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 54, and 62, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 6, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 54 and 62.

[0181] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:1, 7, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 54, and 62, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:1, 7, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 54 and 62.

[0182] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 8, and 40, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 54, and 63, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 8, and 40; and V L The V LIt contains amino acid sequences SEQ ID NOs:48, 54 and 63.

[0183] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:1, 9, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 54, and 64, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:1, 9, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 54 and 64.

[0184] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:3, 10, and 41, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 54, and 62, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:3, 10, and 41; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 54 and 62.

[0185] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 11, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 55, and 65, or the V LVariants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 11, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 55 and 65.

[0186] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 12, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 12, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0187] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 13, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:49, 57, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 13, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:49, 57 and 65.

[0188] In some embodiments, the anti-C5a antibody includes V H The V HContains amino acid sequences SEQ ID NOs:2, 14, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:50, 58, and 66, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 14, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:50, 58 and 66.

[0189] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 15, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 15, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0190] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 16, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 16, and 39; and VL The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0191] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 17, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 17, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0192] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 18, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 18, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0193] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 19, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V LContains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 19, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0194] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 12, and 42, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 12, and 42; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0195] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 12, and 43, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 12, and 43; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0196] In some embodiments, the anti-C5a antibody includes VH The V H Contains amino acid sequences SEQ ID NOs:2, 12, and 44, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 12, and 44; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0197] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 20, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 20, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0198] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 21, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V HContains amino acid sequences SEQ ID NOs:2, 21, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0199] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 22, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 22, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0200] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 23, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 23, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0201] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 24, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The VL Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 24, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0202] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 25, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 25, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0203] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 26, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 26, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0204] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 27, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 27, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0205] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 28, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 28, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0206] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 29, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. HThe V H Contains amino acid sequences SEQ ID NOs:2, 29, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0207] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 30, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 30, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0208] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 31, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:48, 56, and 65, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 31, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:48, 56 and 65.

[0209] In some embodiments, the anti-C5a antibody comprises: V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:80-109 HIncludes HC-CDR1, HC-CDR2, and HC-CDR3, as well as V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:118-124 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0210] In some embodiments, the anti-C5a antibody comprises V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:80. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:81. In some embodiments, the anti-C5a antibody contains V H The V H It comprises one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:82. In some embodiments, the anti-C5a antibody comprises V H The V H It comprises one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:83. In some embodiments, the anti-C5a antibody comprises V H The V H It comprises one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:84. In some embodiments, the anti-C5a antibody comprises V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:85. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:86. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:87. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:88. In some embodiments, the anti-C5a antibody contains V H The V HContains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:89. In some embodiments, the anti-C5a antibody contains V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:90. In some embodiments, the anti-C5a antibody contains V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:91. In some embodiments, the anti-C5a antibody contains V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:92. In some embodiments, the anti-C5a antibody contains V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:93. In some embodiments, the anti-C5a antibody contains V H The V H It comprises one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:94. In some embodiments, the anti-C5a antibody comprises V H The V H It comprises one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:95. In some embodiments, the anti-C5a antibody comprises V H The V H It comprises one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:96. In some embodiments, the anti-C5a antibody comprises V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:97. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:98. In some embodiments, the anti-C5a antibody contains V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:99. In some embodiments, the anti-C5a antibody contains V H The V HContains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:100. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:101. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:102. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:103. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:104. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:105. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:106. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:107. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:108. In some embodiments, the anti-C5a antibody contains V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:109.

[0211] In some embodiments, the anti-C5a antibody comprises V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:118. In some embodiments, the anti-C5a antibody contains V L The V LContains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:119. In some embodiments, the anti-C5a antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:120. In some embodiments, the anti-C5a antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:121. In some embodiments, the anti-C5a antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:123. In some embodiments, the anti-C5a antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:124.

[0212] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:80. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:118. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0213] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:81. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:118. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0214] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:82. HIncludes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:118. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0215] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:83. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:119. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0216] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:84. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:120. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0217] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:85. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:118. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0218] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:86. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:121. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0219] In some embodiments, the anti-C5a antibody comprises V HIt contains V as shown in the amino acid sequence SEQ ID NO:87. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0220] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:88. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:123. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0221] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:89. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:124. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0222] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:90. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0223] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:91. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0224] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:92. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0225] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:93. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0226] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:94. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0227] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:95. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0228] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:96. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. LIt includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0229] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:97. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0230] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:98. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0231] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:99. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0232] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:100. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0233] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:101. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V LIt contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0234] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:102. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0235] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:103. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0236] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:104. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0237] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:105. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0238] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:106. HIncludes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0239] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:107. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0240] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:108. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0241] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:109. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:122. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0242] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:80-109 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:80-109; and V L The V LThe antibody comprises any of the amino acid sequences shown in SEQ ID NOs:118-124 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:118-124. In some embodiments, the anti-C5a antibody comprises V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:80-109, and V L The V L It contains any of the amino acid sequences shown in SEQ ID NOs:118-124.

[0243] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:80 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:80; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:118 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:118. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:80, and V L The V L It contains the amino acid sequence SEQ ID NO:118.

[0244] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:81 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:81; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:118 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:118. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:81, and V L The V L It contains the amino acid sequence SEQ ID NO:118.

[0245] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:82 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:82; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:118 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:118. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:82, and V L The V L It contains the amino acid sequence SEQ ID NO:118.

[0246] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:83 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:83; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:119 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:119. In some embodiments, the anti-C5a antibody comprises V HThe V H Contains the amino acid sequence SEQ ID NO:83, and V L The V L It contains the amino acid sequence SEQ ID NO:119.

[0247] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:84 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:84; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:120 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:120. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:84, and V L The V L It contains the amino acid sequence SEQ ID NO:120.

[0248] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:85 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:85; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:118 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:118. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:85, and V L The V L It contains the amino acid sequence SEQ ID NO:118.

[0249] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:86 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:86; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:121 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:121. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:86, and V L The V L It contains the amino acid sequence SEQ ID NO:121.

[0250] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:87 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:87; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:87, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0251] In some embodiments, the anti-C5a antibody comprises: V H The V HContains the amino acid sequence SEQ ID NO:88 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:88; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:123 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:123. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:88, and V L The V L It contains the amino acid sequence SEQ ID NO:123.

[0252] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:89 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:89; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:124 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:124. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:89, and V L The V L It contains the amino acid sequence SEQ ID NO:124.

[0253] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:90 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:90; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:90, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0254] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:91 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:91; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:91, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0255] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:92 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:92; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V HThe V H Contains the amino acid sequence SEQ ID NO:92, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0256] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:93 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:93; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:93, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0257] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:94 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:94; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:94, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0258] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:95 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:95; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:95, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0259] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:96 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:96; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:96, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0260] In some embodiments, the anti-C5a antibody comprises: V H The V HContains the amino acid sequence SEQ ID NO:97 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:97; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:97, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0261] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:98 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:98; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:98, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0262] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:99 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:99; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:99, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0263] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:100 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:100; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:100, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0264] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:101 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:101; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises VH The V H Contains the amino acid sequence SEQ ID NO:101, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0265] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:102 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:102; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:102, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0266] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:103 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:103; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:103, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0267] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:104 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:104; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:104, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0268] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:105 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:105; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:105, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0269] In some embodiments, the anti-C5a antibody comprises: V H The V HContains the amino acid sequence SEQ ID NO:106 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:106; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:106, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0270] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:107 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:107; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:107, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0271] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:108 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:108; and V L The VL The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:108, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0272] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:109 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:109; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:109, and V L The V L It contains the amino acid sequence SEQ ID NO:122.

[0273] In some embodiments, the anti-C5a antibody includes a heavy chain variable domain (V... H ), the V H It includes: a heavy chain complementarity determination region (HC-CDR)1 containing ELSMH (SEQ ID NO:3); HC-CDR2 containing GFDPX1X2GETIYAQKFQG (SEQ ID NO:72), where X1 is E or R and X2 is D or L; and HC-CDR3 containing GISX1X2WNDAFDI (SEQ ID NO:75), where X1 is D or S and X2 is G, I, or W; and a light chain variable structural domain (V L ), the V LIt includes: light chain complementarity determination region (LC-CDR)1, which includes RASQSVRNDLA (SEQ ID NO:51); LC-CDR2, which includes DASDRAT (SEQ ID NO:59); and LC-CDR3, which includes QQYMDSHPLT (SEQ ID NO:67).

[0274] In some embodiments, the anti-C5a antibody comprises V H The V H It comprises: HC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:3 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); HC-CDR2, which comprises the amino acid sequence shown in any of SEQ ID NOs:32-34 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and HC-CDR3, which comprises the amino acid sequence shown in any of SEQ ID NOs:38-39 and 42 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).

[0275] In some embodiments, the anti-C5a antibody comprises V H The V H It includes: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:3; HC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:32-34; and HC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:38-39 and 42.

[0276] In some embodiments, the anti-C5a antibody comprises V L The V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:51 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:59 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:67 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).

[0277] In some embodiments, the anti-C5a antibody comprises V L The V LIt includes: LC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:51; LC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:59; and LC-CDR3, which contains the amino acid sequence shown in SEQ ID NO:67.

[0278] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:3 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR2, comprising the amino acid sequence shown in any of SEQ ID NOs:32-34 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and HC-CDR3, comprising the amino acid sequence shown in any of SEQ ID NOs:38-39, and 42 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and V L The V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:51 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:59 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:67 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).

[0279] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:3; HC-CDR2, which contains the amino acid sequences shown in any of SEQ ID NOs:32-34; and HC-CDR3, which contains the amino acid sequences shown in any of SEQ ID NOs:38-39 and 42; and V L The V L It comprises: LC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:51; LC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:59; and LC-CDR3, which contains the amino acid sequence shown in SEQ ID NO:67.

[0280] In some embodiments, the anti-C5a antibody comprises V HThe V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:32; HC-CDR3, which contains the amino acid sequence SEQ ID NO:38; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51; LC-CDR2, which contains the amino acid sequence SEQ ID NO:59; LC-CDR3, which contains the amino acid sequence SEQ ID NO:67; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0281] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:32; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:38; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51, LC-CDR2, which contains the amino acid sequence SEQ ID NO:59, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:67.

[0282] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:32; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51; LC-CDR2, which contains the amino acid sequence SEQ ID NO:59; LC-CDR3, which contains the amino acid sequence SEQ ID NO:67; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0283] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:32; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51, LC-CDR2, which contains the amino acid sequence SEQ ID NO:59, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:67.

[0284] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:33; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51; LC-CDR2, which contains the amino acid sequence SEQ ID NO:59; LC-CDR3, which contains the amino acid sequence SEQ ID NO:67; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0285] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:33; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51, LC-CDR2, which contains the amino acid sequence SEQ ID NO:59, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:67.

[0286] In some embodiments, the anti-C5a antibody comprises V H The VH Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:34; HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51; LC-CDR2, which contains the amino acid sequence SEQ ID NO:59; LC-CDR3, which contains the amino acid sequence SEQ ID NO:67; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0287] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:34; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:39; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51, LC-CDR2, which contains the amino acid sequence SEQ ID NO:59, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:67.

[0288] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:32; HC-CDR3, which contains the amino acid sequence SEQ ID NO:42; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51; LC-CDR2, which contains the amino acid sequence SEQ ID NO:59; LC-CDR3, which contains the amino acid sequence SEQ ID NO:67; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0289] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:32; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:42; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:51, LC-CDR2, which contains the amino acid sequence SEQ ID NO:59, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:67.

[0290] In some embodiments, the anti-C5a antibody includes V H The V H Contains any amino acid sequence from SEQ ID NOs:3,32-34,38-39,42 or a variant thereof, said variant, or a substitution comprising up to about 5 amino acids; and V L The V L Contains any amino acid sequence from SEQ ID NOs:51,59,67 or a variant thereof, said variant, or contains substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody comprises V H The V H Contains any amino acid sequence from SEQ ID NOs:3,32-34,38-39,42; and V L The V L It contains any of the amino acid sequences in SEQ ID NOs:51,59,67.

[0291] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:3, 32, and 38, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:51, 59, and 67, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:3, 32, and 38; and V L The V LIt contains amino acid sequences SEQ ID NOs:51, 59 and 67.

[0292] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:3, 32, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:51, 59, and 67, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:3, 32, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:51, 59 and 67.

[0293] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:3, 33, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:51, 59, and 67, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:3, 33, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:51, 59 and 67.

[0294] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:3, 34, and 39, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:51, 59, and 67, or the V LVariants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:3, 34, and 39; and V L The V L It contains amino acid sequences SEQ ID NOs:51, 59 and 67.

[0295] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:3, 32, and 42, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:51, 59, and 67, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:3, 32, and 42; and V L The V L It contains amino acid sequences SEQ ID NOs:51, 59 and 67.

[0296] In some embodiments, the anti-C5a antibody comprises: V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:110-114 H Includes HC-CDR1, HC-CDR2, and HC-CDR3, as well as V L The V L Contains V as shown in SEQ ID NO:125 of the amino acid sequence L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0297] In some embodiments, the anti-C5a antibody comprises V H The V H Contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:110. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:111. In some embodiments, the anti-C5a antibody contains VH The V H Contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:112. In some embodiments, the anti-C5a antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:113. In some embodiments, the anti-C5a antibody contains V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:114.

[0298] In some embodiments, the anti-C5a antibody comprises V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:125.

[0299] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:110. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:125. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0300] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:111. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:125. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0301] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:112. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:125. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0302] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:113. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:125. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0303] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:114. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:125. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0304] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:110-114 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:110-114; and V L The V L The antibody comprises the amino acid sequence shown in SEQ ID NO:125 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence shown in SEQ ID NO:125. In some embodiments, the anti-C5a antibody comprises V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:110-114, and V L The V L It contains the amino acid sequence shown in SEQ ID NO:125.

[0305] In some embodiments, the anti-C5a antibody comprises: V H The V HContains the amino acid sequence SEQ ID NO:110 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:110; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:125 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:125. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:110, and V L The V L It contains the amino acid sequence SEQ ID NO:125.

[0306] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:111 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:111; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:125 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:125. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:111, and V L The V L It contains the amino acid sequence SEQ ID NO:125.

[0307] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:112 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:112; and V L The VL The antibody comprises the amino acid sequence SEQ ID NO:125 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:125. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:112, and V L The V L It contains the amino acid sequence SEQ ID NO:125.

[0308] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:113 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:113; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:125 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:125. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:113, and V L The V L It contains the amino acid sequence SEQ ID NO:125.

[0309] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:114 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:114; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:125 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:125. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:114, and V L The V L It contains the amino acid sequence SEQ ID NO:125.

[0310] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:4; HC-CDR2, which contains the amino acid sequence SEQ ID NO:35; HC-CDR3, which contains the amino acid sequence SEQ ID NO:45; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:52; LC-CDR2, which contains the amino acid sequence SEQ ID NO:60; LC-CDR3, which contains the amino acid sequence SEQ ID NO:68; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0311] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:4; HC-CDR2, which contains the amino acid sequence SEQ ID NO:35; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:45; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:52, LC-CDR2, which contains the amino acid sequence SEQ ID NO:60, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:68.

[0312] In some embodiments, the anti-C5a antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:4, 35, and 45, or the VH Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:52, 60, and 68, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:4, 35, and 45; and V L The V L It contains amino acid sequences SEQ ID NOs:52, 60 and 68.

[0313] In some embodiments, the anti-C5a antibody comprises V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:115.

[0314] In some embodiments, the anti-C5a antibody comprises V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:126.

[0315] In some embodiments, the anti-C5a antibody comprises V as shown in SEQ ID NO:115. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:126. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0316] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:115 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:115; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:126 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:126. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:115, and V L The V L It contains the amino acid sequence SEQ ID NO:126.

[0317] In some embodiments, the anti-C5a antibody includes a heavy chain variable domain (V... H ), the V H It includes: a heavy chain complementarity determination region (HC-CDR)1, which contains NYAIN (SEQ ID NO:5); HC-CDR2, which contains GIX1PFFGX2EDYAQKFQG (SEQ ID NO:73), wherein X1 is V or Y and X2 is T or W; and HC-CDR3, which contains DLLX1GFDI (SEQ ID NO:76), wherein X1 is E or H; and a light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASHDIETWLA (SEQ ID NO:53); LC-CDR2, which includes GASNLQS (SEQ ID NO:61); and LC-CDR3, which includes QQANELPYT (SEQ ID NO:69).

[0318] In some embodiments, the anti-C5a antibody comprises V H The V H It comprises: HC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:5 or a variant thereof, the variant comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; HC-CDR2, which comprises the amino acid sequence shown in any of SEQ ID NOs:36-37 or a variant thereof, the variant comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and HC-CDR3, which comprises the amino acid sequence shown in any of SEQ ID NOs:46-47 or a variant thereof, the variant comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0319] In some embodiments, the anti-C5a antibody comprises V H The V HIt includes: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:5; HC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:36-37; and HC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:46-47.

[0320] In some embodiments, the anti-C5a antibody comprises V L The V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:53 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:61 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:69 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).

[0321] In some embodiments, the anti-C5a antibody comprises V L The V L It includes: LC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:53; LC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:61; and LC-CDR3, which contains the amino acid sequence shown in SEQ ID NO:69.

[0322] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:5 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR2, comprising the amino acid sequence shown in any of SEQ ID NOs:36-37 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and HC-CDR3, comprising the amino acid sequence shown in any of SEQ ID NOs:46-47 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and V L The V LIt comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:53 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:61 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:69 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).

[0323] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:5; HC-CDR2, which contains the amino acid sequences shown in any of SEQ ID NOs:36-37; and HC-CDR3, which contains the amino acid sequences shown in any of SEQ ID NOs:46-47; and V L The V L It comprises: LC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:53; LC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:61; and LC-CDR3, which contains the amino acid sequence shown in SEQ ID NO:69.

[0324] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:5; HC-CDR2, which contains the amino acid sequence SEQ ID NO:36; HC-CDR3, which contains the amino acid sequence SEQ ID NO:46; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:53; LC-CDR2, which contains the amino acid sequence SEQ ID NO:61; LC-CDR3, which contains the amino acid sequence SEQ ID NO:69; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0325] In some embodiments, the anti-C5a antibody comprises V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:5; HC-CDR2, which contains the amino acid sequence SEQ ID NO:36; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:46; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:53, LC-CDR2, which contains the amino acid sequence SEQ ID NO:61, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:69.

[0326] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:5; HC-CDR2, which contains the amino acid sequence SEQ ID NO:37; HC-CDR3, which contains the amino acid sequence SEQ ID NO:47; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:53; LC-CDR2, which contains the amino acid sequence SEQ ID NO:61; LC-CDR3, which contains the amino acid sequence SEQ ID NO:69; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0327] In some embodiments, the anti-C5a antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:5; HC-CDR2, which contains the amino acid sequence SEQ ID NO:37; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:47; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:53, LC-CDR2, which contains the amino acid sequence SEQ ID NO:61, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:69.

[0328] In some embodiments, the anti-C5a antibody includes V H The V HContains any amino acid sequence from SEQ ID NOs:5,36-37,46-47 or a variant thereof, said variant containing substitutions of up to about 5 amino acids; and V L The V L Contains any amino acid sequence from SEQ ID NOs:53,61,69 or a variant thereof, said variant containing substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody comprises V H The V H Contains any amino acid sequence from SEQ ID NOs:5,36-37,46-47; and V L The V L It contains any of the amino acid sequences in SEQ ID NOs:53,61,69.

[0329] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:5, 36, and 46, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:53, 61, and 69, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:5, 36, and 46; and V L The V L It contains amino acid sequences SEQ ID NOs:53, 61 and 69.

[0330] In some embodiments, the anti-C5a antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:5, 37, and 47, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:53, 61, and 69, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-C5a antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:5, 37, and 47; and V L The VL It contains amino acid sequences SEQ ID NOs:53, 61 and 69.

[0331] In some embodiments, the anti-C5a antibody comprises: V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:116-117 H Includes HC-CDR1, HC-CDR2, and HC-CDR3, as well as V L The V L Contains V as shown in SEQ ID NO:127 of the amino acid sequence L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0332] In some embodiments, the anti-C5a antibody comprises V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:116. In some embodiments, the anti-C5a antibody includes V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:117.

[0333] In some embodiments, the anti-C5a antibody comprises V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:127.

[0334] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:116. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:127. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0335] In some embodiments, the anti-C5a antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:117. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:127. LIt includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0336] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:116-117 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:116-117; and V L The V L The antibody comprises the amino acid sequence shown in SEQ ID NO:127 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence shown in SEQ ID NO:127. In some embodiments, the anti-C5a antibody comprises V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:116-117, and V L The V L It contains the amino acid sequence shown in SEQ ID NO:127.

[0337] In some embodiments, the anti-C5a antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:116 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:116; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:127 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:127. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:116, and V L The V L It contains the amino acid sequence SEQ ID NO:127.

[0338] In some embodiments, the anti-C5a antibody comprises: VH The V H Contains the amino acid sequence SEQ ID NO:117 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:117; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:127 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:127. In some embodiments, the anti-C5a antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:117, and V L The V L It contains the amino acid sequence SEQ ID NO:127.

[0339] In some embodiments, the amino acid substitutions described above are limited to the “Exemplary Substitutions” shown in Table 4 herein. In some embodiments, the amino acid substitutions are limited to the “Preferred Substitutions” shown in Table 4 herein.

[0340] In some embodiments, functional epitopes can be resolved using a combined alanine scanning technique. In this process, the combined alanine scanning technique can be used to identify amino acids in the C5a protein essential for interaction with anti-C5a antibodies. In some embodiments, the epitope is conformational, and the epitope can also be identified using the crystal structure of an anti-C5a antibody that binds to the C5a protein.

[0341] In some embodiments, this application provides an antibody that competitively binds to C5a with any of the anti-C5a antibodies described herein. In some embodiments, an antibody capable of competitively binding to an epitope on C5a with any of the anti-C5a antibodies described herein is provided. In some embodiments, an anti-C5a antibody is provided that contains V H and V L The anti-C5a antibody molecule binds to the same epitope, wherein the V H Contains any of the amino acid sequences shown in SEQ ID NOs:80-117, and the V L Contains any of the amino acid sequences shown in SEQ ID NOs:118-127. In some embodiments, an anti-C5a antibody is provided, which, together with V H and V L The anti-C5a antibody competitively binds to C5a, wherein the V HContains any of the amino acid sequences shown in SEQ ID NOs:80-117, and the V L It contains any of the amino acid sequences shown in SEQ ID NOs:118-127.

[0342] In some embodiments, a competition assay can be used to identify monoclonal antibodies that competitively bind to C5a with the anti-C5a antibody described herein. A competition assay can determine whether two antibodies bind to the same epitope by identifying identical or spatially overlapping epitopes or by one antibody competitively inhibiting the binding of another antibody to the antigen. In some embodiments, such a competing antibody binds to the same epitope as the antibody described herein. Some exemplary competition assays include, but are not limited to, conventional assays as described in Harlow and Lane (1988) Antibodies: A Laboratory Manual ch. 14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY). Detailed exemplary methods for resolving antibody-bound epitopes are described in Morris (1996) "Epitope Mapping Protocols," in Methods in Molecular Biology vol. 66 (Humana Press, Totowa, NJ). In some embodiments, if each antibody blocks 50% or more of the binding of another antibody, they are said to bind to the same epitope. In some embodiments, the antibody competing with the anti-C5a antibody described herein is a chimeric antibody, a humanized antibody, or a fully human antibody.

[0343] Exemplary anti-C5a antibody sequences are shown in Tables 2 and 3, where CDRs are numbered according to the Kabat definition. Those skilled in the art will recognize that various known algorithms (Kabat definition) exist for predicting CDR locations and defining the variable regions of the antibody light and heavy chains. CDRs containing antibodies as described herein, V H and / or V L Sequences, but antibodies based on prediction algorithms rather than those exemplified in the table below are also within the scope of this application.

[0344] Table 2. Exemplary anti-C5a antibody CDR sequences

[0345]

[0346]

[0347]

[0348]

[0349] Table 3. Exemplary Sequences

[0350]

[0351]

[0352]

[0353]

[0354] C5a

[0355] The complement system is composed of more than 30 proteins that are activated in response to tissue damage, pathogens, or other foreign invasions. Complement component 5a (C5a) was first described as a cleavage product of complement factor 5 (C5), which possesses chemotactic and anaphylactic properties (Shin et al., 1968). The precursor C5 protein contains 1676 amino acids and has a molecular weight of 188 kDa; its gene is located at 9q33–9q34 (Wetsel et al., 1988). Human C5a is a glycoprotein of approximately 11 kDa containing 74 amino acids, produced by the cleavage of the α-chain of C5 by C5 convertase, but N-linked glycosylation is not essential for its function. The properties of C5a suggest it is an important component of the innate immune response, but current evidence indicates that C5a may also play a role in adaptive immunity (Kohl, 2006). Although C5a is not necessarily a trigger for inflammatory diseases, excessive or uncontrolled C5a is produced in many inflammatory diseases, suggesting that C5a can promote and maintain inflammatory responses (Guo and Ward, 2005). C5a has four antiparallel α-helices linked by peptide rings and is further stabilized by three key disulfide bonds (Monk et al., 2007). Mutagenesis and antibody studies have identified several essential residues that provide interaction with the receptor (Monk et al., 2007 review).

[0356] The complement cascade can be activated via four pathways: the classical pathway, the alternative pathway, the mannan-binding lectin pathway (MBL), or the exogenous protease pathway (Ricklin and Lambris, 2007). The classical and lectin pathways are activated by recognizing antibody complexes formed on pathogen surfaces and mannose on bacterial surfaces, respectively. Both pathways result in serine proteases cleaving C4 to form C4a and C4b. C4b binds to C2, leading to the formation of C2a under the action of the protease. C4b and C2a then form the C3 convertase (C4b2a) in the classical pathway. The alternative pathway can be activated via foreign body surfaces or "slow transport," causing spontaneous hydrolysis of C3, which subsequently binds to factor B to form the C3 convertase (C3bBb) in the alternative pathway. The alternative pathway maintains a low level of complement cascade activation, ensuring a rapid response to invading pathogens (Ricklin and Lambris, 2007). All three pathways described above can lead to the formation of C3 convertases, which further cleave the C3 protein to form C3a and C3b. C3b promotes cellular recognition and clearance of pathogens, and can also combine with C3 convertases (C4b2a or C3bBb) to form C5 convertases (C4b2aC3b or C3bBbC3b). Subsequently, C5 convertases further cleave C5 to produce C5a and C5b. C5b then initiates the assembly of the membrane attack complex (MAC; C5b-9). The complement cascade is tightly regulated by a series of soluble membrane-bound regulatory proteins that prevent complement activation products from targeting host tissues (Ricklin and Lambris, 2007). However, this control can be circumvented through some exogenous pathways, such as thrombin, which can directly cleave C3 and C5, causing activation of the complement system (Amara et al., 2008). Furthermore, activated neutrophils and alveolar macrophages can cleave C5 to produce C5a via secreted serine proteases (Amara et al., 2008). Carboxypeptidases in plasma and on the cell surface can remove the arginine residue from the C-terminus of the protein, thus C5a produced by C5 cleavage can be rapidly metabolized to form C5adesArg (Bokisch and Muller-Eberhard, 1970). Compared to C5a, C5adesArg is less potent, resulting in a lower affinity for the canonical C5a receptor, CD88 (Higginbottom et al., 2005). C5a and C5adesArg are rapidly cleared in vivo, with approximately 50% of C5a and C5adesArg being cleared from circulation within 2–3 minutes. Additionally, some C5a is cleared through binding to CD88 on leukocytes and other cells (Oppermann and Gotze, 1994).However, the second receptor, C5a-like receptor 2 (C5L2), can more effectively remove complement fragments by rapidly internalizing C5a / C5adesArg, particularly C5adesArg, which is then retained and degraded in some cell types (Scola et al. (2009)). Conversely, CD88-expressing cells release a higher proportion of C5a after internalization, and this C5a is undegraded and may still be in an active form. Plasma C5a can also be cleared by the liver (Chenoweth and Goodman, 1983).

[0357] CD88

[0358] C5a binds to both CD88 and C5L2 with similar high affinity. Conversely, C5adesArg has a similar affinity for C5L2 as C5a. However, its affinity with CD88 is much lower. (Monk et al., 2007). CD88 and C5L2 share 35% sequence homology and are located in the same region of chromosome 19 (19q13.3–19q13.4). They cluster with other chemokine receptor genes, such as the formyl peptide receptor family and bradykinin receptor. Both are glycosylated seven-transmembrane proteins with a molecular weight of approximately 45 kDa. CD88 is a G protein-coupled receptor and also a member of the rhodopsin gene family (Monk et al., 2007). It is believed that the binding of C5a to CD88 occurs at two distinct and physically separate sites. The first “recognition” site is located at the extracellular N-terminus (N-terminus) of the receptor, which binds to the core of C5a connected by an N-terminus and disulfide bonds. The second “activation” site is formed by the transmembrane domain of the receptor, which binds to the C-terminus of C5a and leads to the generation of a specific signal transduction pathway mediated by the receptor-coupled G protein (Monk et al., 2007).

[0359] C5L2

[0360] The cell types expressing C5L2 are largely the same as those expressing CD88, including neutrophils, monocytes, lymphocytes, macrophages, and non-myeloid cells (e.g., vascular smooth muscle cells) and tissue-derived cells (e.g., adrenal glands, heart, liver, lungs, spleen, and brain). However, under non-inflammatory conditions, C5L2 expression is significantly lower than CD88 expression (Gao et al., 2005). The function of C5L2 remains unclear. Some experimental data suggest that C5L2 can act as a decoy receptor without signal transduction function. Studies have found that knocking out or blocking C5L2 exacerbates inflammatory responses in mice (Gao et al., 2005; Gerard et al., 2005). This suggests that C5L2 has anti-inflammatory functions, which may work by reducing the amount of C5a that can bind to CD88. Furthermore, C5L2 can act as a positive regulator, at least in mice, where it is crucial for C5a and C3a signaling (Chen et al., 2007). In vitro studies have found that C5L2 is crucial for promoting C5a signaling in neutrophils, macrophages, and fibroblasts, while in vivo C5L2 deficiency can lead to ovalbumin-induced airway hyperresponsiveness and inflammation (Chen et al., 2007). Furthermore, in a mouse model of "late" sepsis (100% lethality), only simultaneous blockade of C5L2 and CD88 provided protection (Rittirsch et al., 2008).

[0361] Full-length anti-C5a antibody

[0362] In some embodiments, the anti-C5a antibody is a full-length anti-C5a antibody. In some embodiments, the full-length anti-C5a antibody is IgA, IgD, IgE, IgG, or IgM. In some embodiments, the full-length anti-C5a antibody includes a constant IgG region, such as a constant region of IgG1, IgG2, IgG3, IgG4, or variants thereof. In some embodiments, the full-length anti-C5a antibody includes a λ light chain constant region. In some embodiments, the full-length anti-C5a antibody includes a κ light chain constant region. In some embodiments, the full-length anti-C5a antibody is a full-length human anti-C5a antibody. In some embodiments, the full-length anti-C5a antibody includes a mouse immunoglobulin Fc sequence. In some embodiments, the full-length anti-C5a antibody includes an altered or otherwise modified Fc sequence such that it has enhanced effector functions of antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

[0363] Therefore, for example, in some embodiments, a full-length anti-C5a antibody comprising an IgG1 constant region is provided, the anti-C5a antibody specifically binding to C5a. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0364] In some embodiments, a full-length anti-C5a antibody comprising an IgG2 constant region is provided, the anti-C5a antibody specifically binding to C5a. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0365] In some embodiments, a full-length anti-C5a antibody comprising an IgG3 constant region is provided, the anti-C5a antibody specifically binding to C5a. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0366] In some embodiments, a full-length anti-C5a antibody comprising an IgG4 constant region is provided, the anti-C5a antibody specifically binding to C5a. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:129. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:129 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:129 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0367] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-5 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:6-37 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:38-47 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising SEQ ID NOs:1-37 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:6 ... The amino acid sequences shown in SEQ ID NOs:48-53 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), LC-CDR2, which contains amino acid sequences shown in SEQ ID NOs:54-61 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and LC-CDR3, which contains amino acid sequences shown in SEQ ID NOs:62-69 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0368] In some embodiments, a full-length anti-C5a antibody comprising an IgG2 constant region is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-5 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:6-37 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:38-47 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising SEQ ID NOs:1-37 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:6-37 or variants thereof, the heavy chain variable domain comprising: HC-CDR2 ... The amino acid sequences shown in SEQ ID NOs:48-53 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); LC-CDR2, which contains amino acid sequences shown in SEQ ID NOs:54-61 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and LC-CDR3, which contains amino acid sequences shown in SEQ ID NOs:62-69 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0369] In some embodiments, a full-length anti-C5a antibody comprising an IgG3 constant region is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-5 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:6-37 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:38-47 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising SEQ ID NOs:1-37 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:6 ... The amino acid sequences shown in SEQ ID NOs:48-53 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); LC-CDR2, which contains amino acid sequences shown in SEQ ID NOs:54-61 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and LC-CDR3, which contains amino acid sequences shown in SEQ ID NOs:62-69 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0370] In some embodiments, a full-length anti-C5a antibody comprising an IgG4 constant region is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-5 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:6-37 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:38-47 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising SEQ ID NOs:1-37 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:6-37 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:6-37 or variants thereof, the heavy chain variable domain comprising: HC-CDR2 ... The amino acid sequences shown in SEQ ID NOs:48-53 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), LC-CDR2, which contains the amino acid sequences shown in SEQ ID NOs:54-61 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), and LC-CDR3, which contains the amino acid sequences shown in SEQ ID NOs:62-69 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:129. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:129 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:129 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0371] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 1-5, HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 6-37, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 38-47, or a variant of the heavy chain variable domain having its HC-CDR sequence comprising substitutions of up to about 5 amino acids (e.g., 1, 2, 3, 4, or 5); and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 48-53, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 54-61, and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 6-5, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 38-47, or a variant of the heavy chain variable domain having its HC-CDR sequence comprising at most about 5 amino acid substitutions (e.g., 1, 2, 3, 4, or 5); and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 48-53, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 54-61, and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 6-5, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 6-5, and HC-CDR3 comprising at most about 5 amino acid substitutions (e.g., 1, 2, 3, 4, or 5); and b) a light The amino acid sequence represented by NOs:62-69, or a variant of the light chain variable domain, contains substitutions of up to about 5 amino acids (e.g., 1, 2, 3, 4, or 5) in its LC-CDR sequence. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0372] In some embodiments, a full-length anti-C5a antibody comprising an IgG4 constant region is provided, wherein the anti-C5a antibody comprises a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 1-5, HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 6-37, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 38-47, or a variant of the heavy chain variable domain having an HC-CDR sequence comprising up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acid substitutions; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 48-53, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 54-61, and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 6-5 ...6-5, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 6-5, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ The amino acid sequence represented by NOs:62-69, or a variant of the light chain variable domain, contains substitutions of up to about 5 amino acids (e.g., 1, 2, 3, 4, or 5) in its LC-CDR sequence. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:129. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:129 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:129 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0373] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:1-5, HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:6-37, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:38-47; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:48-53, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:54-61, and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:62-69. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0374] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG4 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:1-5, HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:6-37, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:38-47; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:48-53, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:54-61, and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:62-69. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:129. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:129 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:129 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0375] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:38; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:48, LC-CDR2 comprising the amino acid sequence SEQ ID NO:54, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:62. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0376] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:6, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:54, and LC-CDR3 comprising amino acid sequence SEQ ID NO:62. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0377] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:7, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:54, and LC-CDR3 comprising amino acid sequence SEQ ID NO:62. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0378] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising amino acid sequence SEQ ID NO:40; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:54, and LC-CDR3 comprising amino acid sequence SEQ ID NO:63. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0379] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:9, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:48, LC-CDR2 comprising the amino acid sequence SEQ ID NO:54, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:64. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0380] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:41; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:48, LC-CDR2 comprising the amino acid sequence SEQ ID NO:54, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:62. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0381] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:11, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:55, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0382] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:12, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:56, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0383] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:13, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:49, LC-CDR2 comprising amino acid sequence SEQ ID NO:57, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0384] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:14, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:50, LC-CDR2 comprising amino acid sequence SEQ ID NO:58, and LC-CDR3 comprising amino acid sequence SEQ ID NO:66. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0385] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:15, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:56, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0386] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:16, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:56, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0387] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:17, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:56, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0388] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:18, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:56, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0389] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:19, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:56, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0390] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:12, and HC-CDR3 comprising amino acid sequence SEQ ID NO:42; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:56, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0391] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:12, and HC-CDR3 comprising amino acid sequence SEQ ID NO:43; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:56, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0392] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:12, and HC-CDR3 comprising amino acid sequence SEQ ID NO:44; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:56, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0393] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:20, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:56, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0394] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:21, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:56, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0395] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:22, and HC-CDR3 comprising amino acid sequence SEQ ID NO:39; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:48, LC-CDR2 comprising amino acid sequence SEQ ID NO:56, and LC-CDR3 comprising amino acid sequence SEQ ID NO:65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:128. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:130. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:131. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:130. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:128 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:131.

[0396] In some embodiments, a full-length anti-C5a antibody comprising a constant region of IgG1 is provided, wherein the anti-C5a antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amin...

Claims

1. An isolated anti-C5a antibody comprising: (i) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 1; HC-CDR2, with the amino acid sequence SEQ ID NO: 6; and HC-CDR3, with the amino acid sequence SEQ ID NO: 38; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 54; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 62; (ii) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 6; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 54; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 62; (iii) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 1; HC-CDR2, with the amino acid sequence SEQ ID NO: 7; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 54; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 62; (iv) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 8; and HC-CDR3, with the amino acid sequence SEQ ID NO: 40; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 54; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 63; (v) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 1; HC-CDR2, with the amino acid sequence SEQ ID NO: 9; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 54; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 64; (vi) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 3; HC-CDR2, with the amino acid sequence SEQ ID NO: 10; and HC-CDR3, with the amino acid sequence SEQ ID NO: 41; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 54; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 62; (vii) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 11; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 55; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (viii) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 12; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (ix) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 13; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 49; LC-CDR2, whose amino acid sequence is SEQ ID NO: 57; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (x) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 14; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 50; LC-CDR2, whose amino acid sequence is SEQ ID NO: 58; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 66; (xi) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 15; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xii) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 16; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xiii) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 17; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xiv) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 18; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xv) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 19; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xvi) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 12; and HC-CDR3, with the amino acid sequence SEQ ID NO: 42; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xvii) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 12; and HC-CDR3, with the amino acid sequence SEQ ID NO: 43; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xviii) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 12; and HC-CDR3, with the amino acid sequence SEQ ID NO: 44; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xix) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 20; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xx) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 21; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xxi) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 22; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xxii) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 23; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xxiii) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 24; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xxiv) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 25; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xxv) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 26; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xxvi) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 27; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xxvii) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 28; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xxviii) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 29; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; (xxix) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 30; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L Contains: LC-CDR1, with the amino acid sequence SEQ ID NO: 48; LC-CDR2, with the amino acid sequence SEQ ID NO: 56; and LC-CDR3, with the amino acid sequence SEQ ID NO: 65; or (xxx) V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 2; HC-CDR2, with the amino acid sequence SEQ ID NO: 31; and HC-CDR3, with the amino acid sequence SEQ ID NO: 39; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 48; LC-CDR2, whose amino acid sequence is SEQ ID NO: 56; and LC-CDR3, whose amino acid sequence is SEQ ID NO: 65; The CDR numbering is based on the Kabat definition.

2. The isolated anti-C5a antibody according to claim 1, comprising: (i) V H Its amino acid sequence is SEQ ID NO: 80 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 80; and V L Its amino acid sequence is SEQ ID NO: 118 or a variant thereof, the variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 118; (ii) V H Its amino acid sequence is SEQ ID NO: 81 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 81; and V L Its amino acid sequence is SEQ ID NO: 118 or a variant thereof, the variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 118; (iii) V H Its amino acid sequence is SEQ ID NO: 82 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 82; and V L Its amino acid sequence is SEQ ID NO: 118 or a variant thereof, the variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 118; (iv) V H Its amino acid sequence is SEQ ID NO: 83 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 83; and V L The amino acid sequence SEQ ID NO: 119 or a variant thereof, wherein the variant has at least 90% sequence identity with the amino acid sequence SEQ ID NO: 119; (v) V H Its amino acid sequence is SEQ ID NO: 84 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 84; and V L Its amino acid sequence is SEQ ID NO: 120 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 120; (vi) V H Its amino acid sequence is SEQ ID NO: 85 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 85; and V L Its amino acid sequence is SEQ ID NO: 118 or a variant thereof, the variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 118; (vii) V H Its amino acid sequence is SEQ ID NO: 86 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 86; and V L The amino acid sequence SEQ ID NO: 121 or a variant thereof, wherein the variant has at least 90% sequence identity with the amino acid sequence SEQ ID NO: 121; (viii) V H Its amino acid sequence is SEQ ID NO: 87 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 87; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (ix) V H Its amino acid sequence is SEQ ID NO: 88 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 88; and V L Its amino acid sequence is SEQ ID NO: 123 or a variant thereof, the variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 123; (x) V H Its amino acid sequence is SEQ ID NO: 89 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 89; and V L Its amino acid sequence is SEQ ID NO: 124 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 124; (xi) V H Its amino acid sequence is SEQ ID NO: 90 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 90; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xii) V H Its amino acid sequence is SEQ ID NO: 91 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 91; and V L It contains the amino acid sequence SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xiii) V H Its amino acid sequence is SEQ ID NO: 92 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 92; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xiv) V H Its amino acid sequence is SEQ ID NO: 93 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 93; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xv) V H Its amino acid sequence is SEQ ID NO: 94 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 94; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xvi) V H Its amino acid sequence is SEQ ID NO: 95 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 95; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xvii) V H Its amino acid sequence is SEQ ID NO: 96 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 96; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xviii) V H Its amino acid sequence is SEQ ID NO: 97 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 97; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xix) V H Its amino acid sequence is SEQ ID NO: 98 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 98; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xx) V H Its amino acid sequence is SEQ ID NO: 99 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 99; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xxi) V H Its amino acid sequence is SEQ ID NO: 100 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 100; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xxii) V H Its amino acid sequence is SEQ ID NO: 101 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 101; and V L It contains the amino acid sequence SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xxiii) V H Its amino acid sequence is SEQ ID NO: 102 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 102; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xxiv) V H Its amino acid sequence is SEQ ID NO: 103 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 103; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xxv) V H Its amino acid sequence is SEQ ID NO: 104 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 104; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xxvi) V H Its amino acid sequence is SEQ ID NO: 105 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 105; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xxvii) V H Its amino acid sequence is SEQ ID NO: 106 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 106; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xxviii) V H Its amino acid sequence is SEQ ID NO: 107 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 107; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; (xxix) V H Its amino acid sequence is SEQ ID NO: 108 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 108; and V L Its amino acid sequence is SEQ ID NO: 122 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 122; or (xxx) V H Its amino acid sequence is SEQ ID NO: 109 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 109; and V L The amino acid sequence is SEQ ID NO: 122 or a variant thereof, the variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO:

122.

3. The anti-C5a antibody isolated according to any one of claims 1-2, wherein the anti-C5a antibody comprises an Fc fragment.

4. The anti-C5a antibody isolated according to claim 3, wherein the anti-C5a antibody is a full-length IgG antibody.

5. The anti-C5a antibody isolated according to claim 4, wherein the anti-C5a antibody is a full-length IgG1, IgG2, IgG3 or IgG4 antibody.

6. The anti-C5a antibody isolated according to any one of claims 1-2, wherein the anti-C5a antibody is a chimeric or fully human antibody.

7. The anti-C5a antibody isolated according to any one of claims 1-2, wherein the anti-C5a antibody is an antigen-binding fragment selected from Fab, Fab', F(ab)'2, Fab'-SH, single-chain antibody, Fv fragment, and double-chain antibody.

8. A nucleic acid molecule encoding the anti-C5a antibody according to any one of claims 1-7.

9. A carrier comprising the nucleic acid molecule of claim 8.

10. An isolated host cell comprising the anti-C5a antibody of any one of claims 1-7, the nucleic acid molecule of claim 8, or the vector of claim 9.

11. A method for preparing anti-C5a antibody, comprising: a) Culture the host cells as described in claim 10 under conditions that enable effective expression of anti-C5a antibodies; and b) Obtain the expressed anti-C5a antibody from the host cell.

12. A pharmaceutical composition comprising an anti-C5a antibody according to any one of claims 1-7, a nucleic acid molecule according to claim 8, a carrier according to claim 9, an isolated host cell according to claim 10, or an antibody prepared by the method according to claim 11, and a pharmaceutically acceptable carrier.

13. The use of any one of the anti-C5a antibodies of claims 1-7, the nucleic acid molecule of claim 8, the vector of claim 9, the isolated host cell of claim 10, the antibody prepared by the method of claim 11, or the pharmaceutical composition of claim 12 in the preparation of a medicament for treating a desired individual disease or condition, wherein the disease or condition is selected from the group consisting of rheumatoid arthritis, inflammatory bowel disease, inflammatory response syndrome (SIRS), ischemia-reperfusion-related injury, acute lung injury, and pneumonia.

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