WO2023129870A2 - ANTIBODIES SPECIFICALLY RECOGNIZING C5aR1 AND USES THEREOF - Google Patents

ANTIBODIES SPECIFICALLY RECOGNIZING C5aR1 AND USES THEREOF Download PDF

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WO2023129870A2
WO2023129870A2 PCT/US2022/082260 US2022082260W WO2023129870A2 WO 2023129870 A2 WO2023129870 A2 WO 2023129870A2 US 2022082260 W US2022082260 W US 2022082260W WO 2023129870 A2 WO2023129870 A2 WO 2023129870A2
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Prior art keywords
amino acid
seq
acid sequence
variant
cdr2
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PCT/US2022/082260
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French (fr)
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WO2023129870A3 (en
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JR. Michael George STRAINIC
Ping Yuan
Chong HE
Wenwu Zhai
Zuoan YI
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Staidson Biopharma Inc.
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Definitions

  • C5a anaphylatoxin chemotactic receptor 1 (C5aR1, also known as CD88) is a member of the rhodopsin superfamily of G-protein-coupled receptor (GPCR) (Gerard NP et al., J Biol Chem 264: 1760-1766, 1989).
  • C5aR with its high affinity ligand C5a, is an essential part of the complement system, playing important role in eliciting the broad immune responses.
  • the structure of C5aR1 conforms to the seven transmembrane receptor family and contains 4 extracellular domains, seven membrane-spanning helices, and 4 intracellular C domians (Dixon et al. Nature 326, 73-77, 1987; Findlay et al. Biochem. J.238, 625-642, 1986).
  • C5aR is a classical G protein-coupled receptor that signals through G ⁇ i and G ⁇ 16 which both are G-proteins.
  • C5aR has been shown to associate with two of the four mammalian ⁇ - arrestins ( ⁇ -arrestin 1, 2), which have different dependencies on the phosphorylation status of the receptor.
  • ⁇ -arrestin 1 mammalian ⁇ - arrestins
  • C5aR undergoes rapid phosphorylation on the six serine residues present in the C-terminal region followed by desensitization and internalization.
  • Serine residues in the C5aR C terminus were identified that control the intracellular trafficking of the C5aR-arrestin complex in response to C5a ⁇ (Braun et al. J Biol Chem. 278:4277-4285, 2003).
  • C5aR1 has been found to be expressed on various inflammatory cells and smooth muscle cells to promote an inflammatory reaction. It is also present on subsets of T cells and dendritic cells to regulate the adaptive immune response (Kemper et al. Nature Rev. Immunol. 7.9-18, 2007). C5a-C5aR interaction is required for the optimal oxidative burst and phagocytosis, which form the fundamental machinery in innate immunity for bacterial clearance. The binding of C5a ligand and its receptor C5aR thereof induces an inflammatory reaction by inducing cytokine and chemokine expression (Monsinjon et al. FASEB J 17:1003–1014, 2003.; Fukuoka et al.
  • C5a-C5aR interaction is also an essential step in neutrophil migration by causing adhesion molecule expression and inducing chemokine production (Riedemann et al. Immunity 19:193–202, 2003.). It has been reported that C5aR1 and its ligand C5a play a key role in initiating and maintaining several inflammatory responses by recruiting and activating neutrophils and monocytes in the lungs (Julien Carvelli et al. Nature 588, 146-150, 2020). In addition, C5a perturbs coagulation and fibrinolysis pathway, resulting in damaging intravascular coagulation (Muhlfelder et al.
  • an isolated anti-C5aR1 antibody comprising: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising SYWMN (SEQ ID NO: 1); an HC-CDR2 comprising RIDPX 1 X 2 X 3 X 4 TRYNQKFED (SEQ ID NO: 72), wherein X 1 is G, R, S, or Y, X 2 is D, R, or S, X 3 is G or S, and X 4 is E or G; and an HC-CDR3 comprising FVX 1 PX 2 GX 3 FX 4 Y (SEQ ID NO: 73), wherein X1 is I or W, X 2 is L, M, Q, S, or V, X3 is A or G, and X4 is A or Q; and a light chain variable domain (V L ) comprising
  • an isolated anti-C5aR1 antibody comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, or a variant thereof comprising up to about 3 amino acid substitutions; an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-15, or a variant thereof comprising up to about 3 amino acid substitutions; and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-31, or a variant thereof comprising up to about 3 amino acid substitutions; and a V L comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-44, or a variant thereof comprising up to about 3 amino acid substitutions; an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NO: 52, or a variant thereof comprising up to about 3 amino acid substitutions; and an LC-CDR3 comprising the amino acid
  • an isolated anti-C5aR1 antibody comprising a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of the V H comprising the amino acid sequence of any one of SEQ ID NOs: 76-91; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of the V L comprising the amino acid sequence of any one of SEQ ID NOs: 104-120.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V H comprising the amino acid sequence of SEQ ID NO: 76; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a V L comprising the amino acid sequence of SEQ ID NO: 104; (ii) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V H comprising the amino acid sequence of SEQ ID NO: 77; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a V L comprising the amino acid sequence of SEQ ID NO: 105; (iii) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V L comprising
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (ii) a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the
  • the isolated anti-C5aR1 antibody comprises: a V H comprising the amino acid sequence of any one of SEQ ID NOs: 76-91, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 76-91; and a V L comprising the amino acid sequence of any one of SEQ ID NOs: 104-120, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 104-120.
  • the isolated anti-C5aR1 antibody comprises: (i) a V H comprising the amino acid sequence of SEQ ID NO: 76, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 76; and a V L comprising the amino acid sequence of SEQ ID NO: 104, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 104; (ii) a V H comprising the amino acid sequence of SEQ ID NO: 77, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 77; and a V L comprising the amino acid sequence of SEQ ID NO: 105, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 105; (iii) a V H comprising the amino acid sequence of SEQ ID NO: 78, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:
  • an isolated anti-C5aR1 antibody comprising: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising SGYSWH (SEQ ID NO: 2); an HC-CDR2 comprising YIHSSGDTDYNPSLKR (SEQ ID NO: 16); and an HC-CDR3 comprising SIGDY (SEQ ID NO: 32); and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 45); an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising SQSTHVPWT (SEQ ID NO: 65).
  • an isolated anti-C5aR1 antibody comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, or a variant thereof comprising up to about 3 amino acid substitutions; an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, or a variant thereof comprising up to about 3 amino acid substitutions; and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant thereof comprising up to about 3 amino acid substitutions; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, or a variant thereof comprising up to about 3 amino acid substitutions; an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof comprising up to about 3 amino acid substitutions; and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 3
  • an isolated anti-C5aR1 antibody comprising a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of the V H comprising the amino acid sequence of any one of SEQ ID NOs: 92-96; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of the V L comprising the amino acid sequence of any one of SEQ ID NOs: 121-127.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V H comprising the amino acid sequence of SEQ ID NO: 92; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a V L comprising the amino acid sequence of SEQ ID NO: 121; (ii) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V H comprising the amino acid sequence of SEQ ID NO: 93; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a V L comprising the amino acid sequence of SEQ ID NO: 122; (iii) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V L comprising
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the isolated anti-C5aR1 antibody comprises: a V H comprising the amino acid sequence of any one of SEQ ID NOs: 92-96, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 92-96; and a V L comprising the amino acid sequence of any one of SEQ ID NOs: 121-127, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 121-127.
  • the isolated anti-C5aR1 antibody comprises: (i) a V H comprising the amino acid sequence of SEQ ID NO: 92, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 92; and a V L comprising the amino acid sequence of SEQ ID NO: 121, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 121; (ii) a V H comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 93; and a V L comprising the amino acid sequence of SEQ ID NO: 122, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 122; (iii) a V H comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V H comprising the amino acid sequence of SEQ ID NO: 97; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a V L comprising the amino acid sequence of SEQ ID NO: 128.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the isolated anti-C5aR1 antibody comprises: a V H comprising the amino acid sequence of SEQ ID NO: 97, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 97; and a V L comprising the amino acid sequence of SEQ ID NO: 128, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 128.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V H comprising the amino acid sequence of SEQ ID NO: 98; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a V L comprising the amino acid sequence of SEQ ID NO: 129.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the isolated anti-C5aR1 antibody comprises: a V H comprising the amino acid sequence of SEQ ID NO: 98, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 98; and a V L comprising the amino acid sequence of SEQ ID NO: 129, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 129.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V H comprising the amino acid sequence of SEQ ID NO: 99; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a V L comprising the amino acid sequence of SEQ ID NO: 130.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the isolated anti-C5aR1 antibody comprises: a V H comprising the amino acid sequence of SEQ ID NO: 99, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 99; and a V L comprising the amino acid sequence of SEQ ID NO: 130, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 130.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V H comprising the amino acid sequence of SEQ ID NO: 100; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a V L comprising the amino acid sequence of SEQ ID NO: 131.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the isolated anti-C5aR1 antibody comprises: a V H comprising the amino acid sequence of SEQ ID NO: 100, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 100; and a V L comprising the amino acid sequence of SEQ ID NO: 131, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 131.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V H comprising the amino acid sequence of SEQ ID NO: 101; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a V L comprising the amino acid sequence of SEQ ID NO: 132.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 48, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the isolated anti-C5aR1 antibody comprises: a V H comprising the amino acid sequence of SEQ ID NO: 101, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 101; and a V L comprising the amino acid sequence of SEQ ID NO: 132, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 132.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V H comprising the amino acid sequence of SEQ ID NO: 102; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a V L comprising the amino acid sequence of SEQ ID NO: 133.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the isolated anti-C5aR1 antibody comprises: a V H comprising the amino acid sequence of SEQ ID NO: 102, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 102; and a V L comprising the amino acid sequence of SEQ ID NO: 133, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 133.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V H comprising the amino acid sequence of SEQ ID NO: 103; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a V L comprising the amino acid sequence of SEQ ID NO: 134.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 50, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the isolated anti-C5aR1 antibody comprises: a V H comprising the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 103; and a V L comprising the amino acid sequence of SEQ ID NO: 134, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 134.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a V H comprising the amino acid sequence of SEQ ID NO: 102; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a V L comprising the amino acid sequence of SEQ ID NO: 135.
  • an isolated anti-C5aR1 antibody comprising: (i) a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the isolated anti-C5aR1 antibody comprises: a V H comprising the amino acid sequence of SEQ ID NO: 102, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 102; and a V L comprising the amino acid sequence of SEQ ID NO: 135, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 135.
  • a V H comprising the amino acid sequence of SEQ ID NO: 102, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 102
  • V L comprising the amino acid sequence of SEQ ID NO: 135, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 135.
  • an isolated anti-C5aR1 antibody that specifically binds to the human C5aR1 with a Kd from about 0.1pM or 1nM.
  • an isolated anti-C5aR1 antibody that specifically binds to C5aR1 competitively with any one of the isolated anti-C5aR1 antibodies described above. In some embodiments, there is provided an isolated anti-C5aR1 antibody that specifically binds to the same epitope as any one of isolated anti-C5aR1 antibodies described above. [0049] In some embodiments according to any of the isolated anti-C5aR1 antibodies described above, the isolated anti-C5aR1 antibody comprises an Fc fragment. In some embodiments, the isolated anti-C5aR1 antibody is a full-length IgG antibody.
  • the isolated anti-C5aR1 antibody is a full-length IgG1, IgG2, IgG3, or IgG4 antibody.
  • the anti-C5aR1 antibody is a chimeric, human, or humanized antibody.
  • the anti-C5aR1 antibody is an antigen binding fragment selected from the group consisting of a Fab, a Fab', a F(ab)' 2 , a Fab'-SH, a single- chain Fv (scFv), an Fv fragment, a dAb, a Fd, a nanobody, a diabody, and a linear antibody.
  • nucleic acid molecule(s) that encodes any one of the anti-C5aR1 antibodies described above.
  • a vector comprising any one of the nucleic acid molecules described above.
  • a host cell comprising any one of the anti-C5aR1 antibodies described above, any one of the nucleic acid molecules described above, or any one of the vectors described above.
  • a method of producing an anti-C5aR1 antibody comprising: a) culturing any one of the host cells described above under conditions effective to express the anti-C5aR1 antibody; and b) obtaining the expressed anti-C5aR1 antibody from the host cell.
  • a method of treating a disease or condition in an individual in need thereof comprising administering to the individual an effective amount of any one of the anti-C5aR1 antibodies described above.
  • the disease or condition is associated with C5aR1, comprising inflammatory diseases, autoimmune disease, or cancers or condition.
  • the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies.
  • FIG.1A shows the binding affinity of exemplary hybridoma and chimeric anti-C5aR1 antibodies 10G1 and 1C2 to human C5aR1 as analyzed by FACS.
  • FIG.1B shows the inhibition of C5aR1 function by exemplary hybridoma and chimeric anti-C5aR1 antibodies 10G1 and 1C2 as analyzed by C5aR1-TEV/ ⁇ -Arrestin-Luc reporter assay ⁇
  • FIGS.2A-2B show the binding affinity of an exemplary humanized anti-C5aR1 antibody 1C2.35 to human C5aR1as analyzed by FACS.
  • FIG.3 shows the ligand blocking assay of exemplary humanized anti-C5aR1 antibody 1C2.35 that blocks C5a binding to C5aR1 as analyzed by FACS.
  • FIGS.4A-4B show the inhibition of C5aR1 function by an exemplary humanized anti- C5aR1 antibodies 1C2.35 as analyzed by C5aR1-TEV/ ⁇ -Arrestin-Luc reporter assay ⁇
  • FIGS.5A-5B show the inhibition of C5a-induced upregulation of neutrophil CD11b by an exemplary humanized anti-C5aR1 antibody 1C2.35.
  • FIGS.6A-6B show the binding affinity of an exemplary humanized anti-C5aR1 antibody 10G1.44 to human C5aR1 as analyzed by FACS.
  • FIGS.7A-7B show the inhibition of C5a-induced upregulation of neutrophil CD11b by an exemplary humanized anti-C5aR1 antibody 10G1.44.
  • FIGS.8A-8D show the in vivo anti-autoimmune efficacy results of exemplary anti- C5aR1 antibody 1C2 in murine model of imiquimod-induced psoriasis.
  • FIG.8A shows the H&E staining results for skin thickness and scales from psoriatic skin lesions samples after treatment of exemplary anti-C5aR1 antibody 1C2 or reference antibody.
  • FIG.8B shows the epidermal thickness quantification result from psoriatic skin lesions samples after treatment of exemplary anti-C5aR1 antibody 1C2 or reference antibody.
  • FIG.8C shows the psoriasis area severity index (PASI) total score result of exemplary anti-C5aR1 antibody 1C2 or the reference antibody after IMQ treatment.
  • FIG.8D shows a schematic diagram of experimental protocol including prophylactic anti-C5aR1 antibody treatment, followed by disease induction by IMQ treatment and collection and recording of the parameters during and after the experiment.
  • PASI psoriasis area severity index
  • the present application in one aspect provides an isolated anti-C5aR1 antibody that specifically binds to human and/or cynomolgus monkey C5aR1.
  • an isolated anti-C5aR1 antibody that specifically binds to human and/or cynomolgus monkey C5aR1.
  • the anti-C5aR1 antibodies provided by the present application include, for example, full-length anti-C5aR1 antibodies, anti-C5aR1 scFvs, anti-C5aR1 Fc fusion proteins, multi- specific (such as bispecific) anti-C5aR1 antibodies, anti-C5aR1 immunoconjugates, and the like.
  • the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising SYWMN (SEQ ID NO: 1); an HC-CDR2 comprising RIDPX 1 X 2 X 3 X 4 TRYNQKFED (SEQ ID NO: 72), wherein X 1 is G, R, S, or Y, X 2 is D, R, or S, X 3 is G or S, and X 4 is E or G; and an HC-CDR3 comprising FVX 1 PX 2 GX 3 FX 4 Y (SEQ ID NO: 73), wherein X 1 is I or W, X 2 is L, M, Q, S, or V, X 3 is A or G, and X 4 is A or Q; and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising SYWMN (SEQ
  • the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising SGYSWH (SEQ ID NO: 2); an HC-CDR2 comprising YIHSSGDTDYNPSLKR (SEQ ID NO: 16); and an HC-CDR3 comprising SIGDY (SEQ ID NO: 32); and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 45); an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising SQSTHVPWT (SEQ ID NO: 65).
  • V H heavy chain variable domain
  • HC- CDR heavy chain complementarity determining region
  • the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising SGYSWH (SEQ ID NO: 2); an HC-CDR2 comprising YTHNSGDTNYSPSLKR (SEQ ID NO: 17); and an HC-CDR3 comprising SVGDY (SEQ ID NO: 33); and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 45); an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising SQSTHVPWT (SEQ ID NO: 65).
  • V H heavy chain variable domain
  • HC- CDR heavy chain complementarity determining region
  • the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising NYWMN (SEQ ID NO: 3); an HC-CDR2 comprising RIDPSDSETRYNQKFKD (SEQ ID NO: 18); and an HC-CDR3 comprising YGWLRGYYAMDY (SEQ ID NO: 34); and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTHLH (SEQ ID NO: 46); an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising SQSTLVPLT (SEQ ID NO: 66).
  • V H heavy chain variable domain
  • HC- CDR heavy chain complementarity determining region
  • the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising TGYSWH (SEQ ID NO: 4); an HC-CDR2 comprising YIHSSGRTDYNPSLKS (SEQ ID NO: 19); and an HC-CDR3 comprising SVGDY (SEQ ID NO: 33); and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 45); an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising SQSTHVPWT (SEQ ID NO: 65).
  • V H heavy chain variable domain
  • HC- CDR heavy chain complementarity determining region
  • the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising GYYMH (SEQ ID NO: 5); an HC-CDR2 comprising RVYPYNGVTAYNQNFKD (SEQ ID NO: 20); and an HC-CDR3 comprising RGLRNYGDDPWFAY (SEQ ID NO: 35); and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RASSSVSYMH (SEQ ID NO: 47); an LC-CDR2 comprising ATSNLAS (SEQ ID NO: 53); and an LC-CDR3 comprising QQWSSNPPT (SEQ ID NO: 67).
  • V H heavy chain variable domain
  • HC- CDR heavy chain complementarity determining region
  • the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising GSWMN (SEQ ID NO: 6); an HC-CDR2 comprising RIYPGDGNTKYSGKFKD (SEQ ID NO: 21); and an HC-CDR3 comprising DYPYYVDY (SEQ ID NO: 36); and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLENSNGNTYLN (SEQ ID NO: 48); an LC-CDR2 comprising RVSNRFS (SEQ ID NO: 54); and an LC-CDR3 comprising LQLTHVPPT (SEQ ID NO: 68).
  • V H heavy chain variable domain
  • HC- CDR heavy chain complementarity determining region
  • GSWMN SEQ ID NO: 6
  • an HC-CDR2 comprising
  • the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising SYWMN (SEQ ID NO: 1); an HC-CDR2 comprising RIDPFDSETRYNQKFKD (SEQ ID NO: 22); and an HC-CDR3 comprising ITTGPWFAY (SEQ ID NO: 37); and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RASQDISNYLN (SEQ ID NO: 49); an LC-CDR2 comprising YTSRLHS (SEQ ID NO: 55); and an LC-CDR3 comprising QQGNTLPPT (SEQ ID NO: 69).
  • V H heavy chain variable domain
  • HC- CDR heavy chain complementarity determining region
  • the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising SDYAWN (SEQ ID NO: 7); an HC-CDR2 comprising YISYSGDTSYNPSLKS (SEQ ID NO: 23); and an HC-CDR3 comprising AGRRGFDY (SEQ ID NO: 38); and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RASQSISNYLH (SEQ ID NO: 50); an LC-CDR2 comprising YASQSIS (SEQ ID NO: 56); and an LC-CDR3 comprising QQSNSWPIFT (SEQ ID NO: 70).
  • V H heavy chain variable domain
  • HC- CDR heavy chain complementarity determining region
  • HC- CDR heavy chain complementarity determining region
  • SDYAWN SEQ ID NO: 7
  • the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising SYWMN (SEQ ID NO: 1); an HC-CDR2 comprising RIDPFDSETRYNQKFKD (SEQ ID NO: 22); and an HC-CDR3 comprising ITTGPWFAY (SEQ ID NO: 37); and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising SASQGISNYLN (SEQ ID NO: 51); an LC-CDR2 comprising YTSSLHS (SEQ ID NO: 57); and an LC-CDR3 comprising QQYSKLPPT (SEQ ID NO: 71).
  • V H heavy chain variable domain
  • HC- CDR heavy chain complementarity determining region
  • nucleic acids encoding the anti-C5aR1 antibodies are also provided.
  • compositions comprising the anti-C5aR1 antibodies are also provided.
  • methods of making and using the anti-C5aR1 antibodies are also provided.
  • treatment or “treating” is an approach for obtaining beneficial or desired results, including clinical results.
  • beneficial or desired clinical results include, but are not limited to, one or more of the following: alleviating one or more symptoms resulting from the disease, diminishing the extent of the disease, stabilizing the disease (e.g., preventing or delaying the worsening of the disease), preventing or delaying the spread (e.g., metastasis) of the disease, preventing or delaying the recurrence of the disease, delaying or slowing the progression of the disease, ameliorating the disease state, providing a remission (partial or total) of the disease, decreasing the dose of one or more of other medications required to treat the disease, delaying the progression of the disease, increasing or improving the quality of life, increasing weight gain, and/or prolonging survival.
  • antibody includes full-length antibodies and antigen-binding fragments thereof.
  • a full-length antibody comprises two heavy chains and two light chains. The variable regions of the light and heavy chains are responsible for antigen binding.
  • variable regions in both chains generally contain three highly variable loops called the complementarity determining regions (CDRs) (light chain (LC) CDRs including LC-CDR1, LC-CDR2, and LC-CDR3, heavy chain (HC) CDRs including HC-CDR1, HC-CDR2, and HC-CDR3).
  • CDR boundaries for the antibodies and antigen-binding fragments disclosed herein may be defined or identified by the conventions of Kabat, Chothia, or Al-Lazikani (Al- Lazikani 1997; Chothia 1985; Chothia 1987; Chothia 1989; Kabat 1987; Kabat 1991).
  • the three CDRs of the heavy or light chains are interposed between flanking stretches known as framework regions (FRs), which are more highly conserved than the CDRs and form a scaffold to support the hypervariable loops.
  • the constant regions of the heavy and light chains are not involved in antigen binding, but exhibit various effector functions.
  • Antibodies are assigned to classes based on the amino acid sequence of the constant region of their heavy chain.
  • the five major classes or isotypes of antibodies are IgA, IgD, IgE, IgG, and IgM, which are characterized by the presence of ⁇ , ⁇ , ⁇ , ⁇ , and ⁇ heavy chains, respectively.
  • IgG1 ⁇ 1 heavy chain
  • IgG2 ⁇ 2 heavy chain
  • IgG3 ⁇ 3 heavy chain
  • IgG4 ⁇ 4 heavy chain
  • IgA1 ⁇ 1 heavy chain
  • IgA2 ⁇ 2 heavy chain
  • antigen-binding fragment includes an antibody fragment including, for example, a diabody, a Fab, a Fab', a F(ab') 2 , an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv) 2 , a bispecific dsFv (dsFv-dsFv'), a disulfide stabilized diabody (ds diabody), a single-chain Fv (scFv), an scFv dimer (bivalent diabody), a multispecific antibody formed from a portion of an antibody comprising one or more CDRs, a single domain antibody, a nanobody, a domain antibody, a bivalent domain antibody, or any other antibody fragments that bind to an antigen but do not comprise a complete antibody structure.
  • an antibody fragment including, for example, a diabody, a Fab, a Fab', a F(ab') 2 , an Fv fragment
  • An antigen-binding fragment also includes a fusion protein comprising the antibody fragment described above.
  • An antigen-binding fragment is capable of binding to the same antigen to which the parent antibody or a parent antibody fragment (e.g., a parent scFv) binds.
  • an antigen-binding fragment may comprise one or more CDRs from a particular human antibody grafted to a framework region from one or more different human antibodies.
  • epitope refers to the specific group of atoms or amino acids on an antigen to which an antibody or antibody moiety binds. Two antibodies or antibody moieties may bind the same epitope within an antigen if they exhibit competitive binding for the antigen.
  • a first antibody "competes" for binding to a target C5aR1 with a second antibody when the first antibody inhibits target C5aR1 binding of the second antibody by at least about 50% (such as at least about any of 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99%) in the presence of an equimolar concentration of the first antibody, or vice versa.
  • a high throughput process for "binning" antibodies based upon their cross- competition is described in PCT Publication No. WO 03/48731.
  • the term “specifically binds”, “specifically recognizing”, or “is specific for” refers to measurable and reproducible interactions, such as binding between a target and an antibody that is determinative of the presence of the target in the presence of a heterogeneous population of molecules, including biological molecules.
  • an antibody that specifically recognizes a target (which can be an epitope) is an antibody that binds to this target with greater affinity, avidity, more readily, and/or with greater duration than its binding to other targets.
  • an antibody that specifically recognizes an antigen reacts with one or more antigenic determinants of the antigen with a binding affinity that is at least about 10 times its binding affinity for other targets.
  • An "isolated" anti-C5aR1 antibody as used herein refers to an anti-C5aR1 antibody that (1) is not associated with proteins found in nature, (2) is free of other proteins from the same source, (3) is expressed by a cell from a different species, or, (4) does not occur in nature.
  • isolated nucleic acid as used herein is intended to mean a nucleic acid of genomic, cDNA, or synthetic origin or some combination thereof, which by virtue of its origin the "isolated nucleic acid” (1) is not associated with all or a portion of a polynucleotide in which the "isolated nucleic acid” is found in nature, (2) is operably linked to a polynucleotide which it is not linked to in nature, or (3) does not occur in nature as part of a larger sequence.
  • CDR complementary metal-determining region
  • chimeric antibody refers to an antibody in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit a biological activity of this application (see U.S. Patent No.4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)).
  • Fv is the minimum antibody fragment which contains a complete antigen- recognition and binding site. This fragment consists of a dimer of one heavy- and one light- chain variable region domain in tight, non-covalent association. From the folding of these two domains emanate six hypervariable loops (3 loops each from the heavy and light chain) that contribute the amino acid residues for antigen binding and confer antigen binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.
  • Single-chain Fv also abbreviated as “sFv” or “scFv”
  • sFv single-chain Fv
  • the scFv polypeptide further comprises a polypeptide linker between the V H and V L domains which enables the scFv to form the desired structure for antigen binding.
  • diabodies refers to small antibody fragments prepared by constructing scFv fragments (see preceding paragraph) typically with short linkers (such as about 5 to about 10 residues) between the V H and V L domains such that inter-chain but not intra-chain pairing of the V domains is achieved, resulting in a bivalent fragment, i.e., fragment having two antigen-binding sites.
  • Bispecific diabodies are heterodimers of two "crossover" scFv fragments in which the V H and V L domains of the two antibodies are present on different polypeptide chains.
  • Diabodies are described more fully in, for example, EP 404,097; WO 93/11161; and Hollinger et al., Proc.
  • Humanized forms of non-human (e.g., rodent) antibodies are chimeric antibodies that contain minimal sequence derived from the non-human antibody.
  • humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a hypervariable region (HVR) of the recipient are replaced by residues from a hypervariable region of a non-human species (donor antibody) such as mouse, rat, rabbit or non-human primate having the desired antibody specificity, affinity, and capability.
  • donor antibody such as mouse, rat, rabbit or non-human primate having the desired antibody specificity, affinity, and capability.
  • framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues.
  • humanized antibodies can comprise residues that are not found in the recipient antibody or in the donor antibody. These modifications are made to further refine antibody performance.
  • the humanized antibody will comprise substantially at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the FRs are those of a human immunoglobulin sequence.
  • the humanized antibody optionally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin.
  • Fc immunoglobulin constant region
  • Percent (%) amino acid sequence identity or "homology” with respect to the polypeptide and antibody sequences identified herein is defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the polypeptide being compared, after aligning the sequences considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skilled in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), or MUSCLE software.
  • % amino acid sequence identity values are generated using the sequence comparison computer program MUSCLE (Edgar, R.C., Nucleic Acids Research 32(5):1792-1797, 2004; Edgar, R.C., BMC Bioinformatics 5(1):113, 2004).
  • MUSCLE sequence comparison computer program
  • an FcR of this application is one that binds to an IgG antibody (a ⁇ receptor) and includes receptors of the Fc ⁇ RI, Fc ⁇ RII, and Fc ⁇ RIII subclasses, including allelic variants and alternatively spliced forms of these receptors.
  • Fc ⁇ RII receptors include Fc ⁇ RIIA (an “activating receptor”) and Fc ⁇ RIIB (an “inhibiting receptor”), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof.
  • Activating receptor Fc ⁇ RIIA contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain.
  • ITAM immunoreceptor tyrosine-based activation motif
  • Inhibiting receptor Fc ⁇ RIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain (see review M. in Da ⁇ ron, Annu. Rev. Immunol.15:203-234 (1997)).
  • the term includes allotypes, such as Fc ⁇ RIIIA allotypes: Fc ⁇ RIIIA-Phe158, Fc ⁇ RIIIA-Val158, Fc ⁇ RIIA-R131 and/or Fc ⁇ RIIA-H131.
  • FcRs are reviewed in Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991); Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J. Lab.
  • FcR FcR
  • FcRn the neonatal receptor
  • FcRn is structurally similar to major histocompatibility complex (MHC) and consists of an ⁇ -chain noncovalently bound to ⁇ 2-microglobulin.
  • MHC major histocompatibility complex
  • FcRn plays a role in the passive delivery of immunoglobulin IgGs from mother to young and the regulation of serum IgG levels.
  • FcRn can act as a salvage receptor, binding and transporting pinocytosed IgGs in intact form both within and across cells, and rescuing them from a default degradative pathway.
  • the "CH1 domain" of a human IgG Fc region usually extends from about amino acid 118 to about amino acid 215 (EU numbering system).
  • "Hinge region” is generally defined as stretching from Glu216 to Pro230 of human IgG1 (Burton, Molec. Immunol.22:161-206 (1985)). Hinge regions of other IgG isotypes may be aligned with the IgG1 sequence by placing the first and last cysteine residues forming inter-heavy chain S-S bonds in the same positions.
  • the "CH2 domain" of a human IgG Fc region usually extends from about amino acid 231 to about amino acid 340.
  • the CH2 domain is unique in that it is not closely paired with another domain. Rather, two N-linked branched carbohydrate chains are interposed between the two CH2 domains of an intact native IgG molecule. It has been speculated that the carbohydrate may provide a substitute for the domain-domain pairing and help stabilize the CH2 domain. Burton, Molec Immunol.22:161-206 (1985). [0094]
  • the "CH3 domain” comprises the stretch of residues of C-terminal to a CH2 domain in an Fc region (i.e. from about amino acid residue 341 to the C-terminal end of an antibody sequence, typically at amino acid residue 446 or 447 of an IgG).
  • a "functional Fc fragment” possesses an "effector function” of a native sequence Fc region.
  • effector functions include C1q binding; complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor; BCR), etc.
  • Such effector functions generally require the Fc region to be combined with a binding domain (e.g., an antibody variable domain) and can be assessed using various assays known in the art.
  • An antibody with a variant IgG Fc with "altered" FcR binding affinity or ADCC activity is one which has either enhanced or diminished FcR binding activity (e.g., Fc ⁇ R or FcRn) and/or ADCC activity compared to a parent polypeptide or to a polypeptide comprising a native sequence Fc region.
  • the variant Fc which "exhibits increased binding" to an FcR binds at least one FcR with higher affinity (e.g., lower apparent Kd or IC 50 value) than the parent polypeptide or a native sequence IgG Fc.
  • the improvement in binding compared to a parent polypeptide is about 3-fold, such as about any of 5, 10, 25, 50, 60, 100, 150, 200, or up to 500-fold, or about 25% to 1000% improvement in binding.
  • the polypeptide variant which "exhibits decreased binding" to an FcR binds at least one FcR with lower affinity (e.g., higher apparent Kd or IC 50 value) than a parent polypeptide.
  • the decrease in binding compared to a parent polypeptide may be about 40% or more decrease in binding.
  • ADCC antibody-dependent cell-mediated cytotoxicity
  • FcRs Fc receptors
  • cytotoxic cells e.g., Natural Killer (NK) cells, neutrophils, and macrophages
  • NK cells Natural Killer cells
  • neutrophils neutrophils
  • macrophages cytotoxic cells
  • the antibodies “arm” the cytotoxic cells and are required for such killing.
  • the primary cells for mediating ADCC, NK cells express Fc ⁇ RIII only, whereas monocytes express Fc ⁇ RI, Fc ⁇ RII and Fc ⁇ RIII.
  • ADCC activity of a molecule of interest is assessed in vivo, e.g., in an animal model such as that disclosed in Clynes et al. PNAS (USA) 95:652-656 (1998).
  • the polypeptide comprising a variant Fc region which "exhibits increased ADCC" or mediates ADCC in the presence of human effector cells more effectively than a polypeptide having wild type IgG Fc or a parent polypeptide is one which in vitro or in vivo is substantially more effective at mediating ADCC, when the amounts of polypeptide with variant Fc region and the polypeptide with wild type Fc region (or the parent polypeptide) in the assay are essentially the same.
  • such variants will be identified using any in vitro ADCC assay known in the art, such as assays or methods for determining ADCC activity, e.g., in an animal model etc.
  • the variant is from about 5-fold to about 100-fold, e.g. from about 25 to about 50-fold, more effective at mediating ADCC than the wild type Fc (or parent polypeptide).
  • “Complement dependent cytotoxicity” or “CDC” refers to the lysis of a target cell 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 antibodies (of the appropriate subclass) which are bound to their cognate antigen.
  • C1q the first component of the complement system
  • a CDC assay e.g. as described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996), may be performed.
  • nucleotide sequence encoding an amino acid sequence includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence.
  • nucleotide sequence that encodes a protein or a RNA may also include introns to the extent that the nucleotide sequence encoding the protein may in some version contain an intron(s).
  • operably linked refers to functional linkage between a regulatory sequence and a heterologous nucleic acid sequence resulting in expression of the latter.
  • a first nucleic acid sequence is operably linked with a second nucleic acid sequence when the first nucleic acid sequence is placed in a functional relationship with the second nucleic acid sequence.
  • a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence.
  • operably linked DNA sequences are contiguous and, where necessary to join two protein coding regions, in the same reading frame.
  • "Homologous" refers to the sequence similarity or sequence identity between two polypeptides or between two nucleic acid molecules.
  • the molecules are homologous at that position.
  • the percent of homology between two sequences is a function of the number of matching or homologous positions shared by the two sequences divided by the number of positions compared times 100. For example, if 6 of 10 of the positions in two sequences are matched or homologous then the two sequences are 60% homologous.
  • the DNA sequences ATTGCC and TATGGC share 50% homology. Generally, a comparison is made when two sequences are aligned to give maximum homology.
  • an “effective amount” of an anti-C5aR1 antibody or composition as disclosed herein is an amount sufficient to carry out a specifically stated purpose.
  • An “effective amount” can be determined empirically and by known methods relating to the stated purpose.
  • the term “therapeutically effective amount” refers to an amount of an anti- C5aR1 antibody or composition as disclosed herein, effective to "treat” a disease or disorder in an individual.
  • the therapeutically effective amount of the anti-C5aR1 antibody or composition as disclosed herein can reduce the number of cancer cells; reduce the tumor size or weight; inhibit (i.e., slow to some extent and preferably stop) cancer cell infiltration into peripheral organs; inhibit (i.e., slow to some extent and preferably stop) tumor metastasis; inhibit, to some extent, tumor growth; and/or relieve to some extent one or more of the symptoms associated with the cancer.
  • the anti-C5aR1 antibody or composition as disclosed herein can prevent growth and/or kill existing cancer cells, it can be cytostatic and/or cytotoxic.
  • the therapeutically effective amount is a growth inhibitory amount.
  • the therapeutically effective amount is an amount that extends the survival of a patient. In some embodiments, the therapeutically effective amount is an amount that improves progression free survival of a patient.
  • pharmaceutically acceptable or “pharmacologically compatible” is meant a material that is not biological or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition administered to a patient without causing any significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained.
  • Pharmaceutically acceptable carriers or excipients have preferably met the required standards of toxicological and manufacturing testing and/or are included on the Inactive Ingredient Guide prepared by the U.S. Food and Drug Administration.
  • Anti-C5aR1 antibodies [00110] In one aspect, the present application provides anti-C5aR1 antibodies that specifically bind to human and/or cynomolgus monkey C5aR1. Anti-C5aR1 antibodies include, but are not limited to, humanized antibodies, chimeric antibodies, mouse antibodies, human antibodies, and antibodies comprising the heavy chain and/or light chain CDRs discussed herein. In one aspect, the present application provides isolated antibodies that bind to C5aR1.
  • Contemplated anti-C5aR1 antibodies include, for example, full-length anti-C5aR1 antibodies (e.g., full-length IgG1 or IgG4), anti-C5aR1 scFvs, anti-C5aR1 Fc fusion proteins, multi-specific (such as bispecific) anti-C5aR1 antibodies, anti-C5aR1 immunoconjugates, and the like.
  • the anti-C5aR1 antibody is a full-length antibody (e.g., full-length IgG1 or IgG4) or antigen-binding fragment thereof, which specifically binds to C5aR1.
  • the anti-C5aR1 antibody is a Fab, a Fab', a F(ab)' 2 , a Fab'-SH, a single-chain Fv (scFv), an Fv fragment, a dAb, a Fd,a nanobody, a diabody, or a linear antibody.
  • reference to an antibody that specifically binds to C5aR1 means that the antibody binds to C5aR1 with an affinity that is at least about 10 times (including for example at least about any one of 10, 10 2 , 10 3 , 10 4 , 10 5 , 10 6 , or 10 7 times) more tightly than its binding affinity for a non-target.
  • the non-target is an antigen that is not C5aR1.
  • Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence activated cell sorting (FACS) analysis, or radioimmunoprecipitation assay (RIA).
  • Kd can be determined by methods known in the art, such as surface plasmon resonance (SPR) assay or biolayer interferometry (BLI).
  • SPR surface plasmon resonance
  • BBI biolayer interferometry
  • non-human anti-C5aR1 antibodies comprise human CDR sequences from an anti-C5aR1 antibody as described herein and non-human framework sequences.
  • Non-human framework sequences include, in some embodiments, any sequence that can be used for generating synthetic heavy and/or light chain variable domains using one or more human CDR sequences as described herein, including, e.g., mammals, e.g., mouse, rat, rabbit, pig, bovine (e.g., cow, bull, buffalo), deer, sheep, goat, chicken, cat, dog, ferret, primate (e.g., marmoset, rhesus monkey), etc.
  • mammals e.g., mouse, rat, rabbit, pig, bovine (e.g., cow, bull, buffalo), deer, sheep, goat, chicken, cat, dog, ferret, primate (e.g., marmoset, rhesus monkey), etc.
  • a non-human anti-C5aR1 antibody includes an anti-C5aR1 antibody generated by grafting one or more human CDR sequences as described herein onto a non-human framework sequence (e.g., a mouse or chicken framework sequence).
  • a non-human framework sequence e.g., a mouse or chicken framework sequence.
  • the complete amino acid sequence of an exemplary native human C5aR1 comprises or consists of the amino acid sequence of SEQ ID NO: 140.
  • the complete amino acid sequence of an exemplary native musculus C5aR1 comprises or consists of the amino acid sequence of SEQ ID NO: 141.
  • the complete amino acid sequence of an exemplary native cynomolgus monkey C5aR1 comprises or consists of the amino acid sequence of SEQ ID NO: 142.
  • the anti-C5aR1 antibody described herein specifically recognizes an epitope within human C5aR1. In some embodiments, the anti-C5aR1 antibody cross-reacts with C5aR1 from species other than human. In some embodiments, the anti- C5aR1 antibody is completely specific for human C5aR1 and does not exhibit cross- reactivity with C5aR1s from other non-human species. [00114] In some embodiments, the anti-C5aR1 antibody cross-reacts with at least one allelic variant of the C5aR1 protein (or fragments thereof).
  • the allelic variant has up to about 30 (such as about any of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30) amino acid substitutions (such as a conservative substitution) when compared to the naturally occurring C5aR1 (or fragments thereof).
  • the anti-C5aR1 antibody does not cross-react with any allelic variants of the C5aR1 protein (or fragments thereof).
  • the anti-C5aR1 antibody cross-reacts with at least one interspecies variant of the C5aR1 protein.
  • the C5aR1 protein (or fragments thereof) is human C5aR1 and the interspecies variant of the C5aR1 protein (or fragments thereof) is a cynomolgus monkey variant thereof.
  • the anti-C5aR1 antibody does not cross-react with any interspecies variants of the C5aR1 protein.
  • the anti-C5aR1 antibody comprises an antibody heavy chain constant region and an antibody light chain constant region.
  • the anti-C5aR1 antibody comprises an IgG1 heavy chain constant region.
  • the anti-C5aR1 antibody comprises an IgG2 heavy chain constant region. In some embodiments, the anti- C5aR1 antibody comprises an IgG3 heavy chain constant region. In some embodiments, the anti-C5aR1 antibody comprises an IgG4 heavy chain constant region. In some embodiments, the heavy chain constant region comprises (including consisting of or consisting essentially of) the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises (including consisting of or consisting essentially of) the amino acid sequence of SEQ ID NO: 137. In some embodiments, the anti-C5aR1 antibody comprises a kappa light chain constant region.
  • the light chain constant region comprises (including consisting of or consisting essentially of) the amino acid sequence of SEQ ID NO: 138.
  • the anti-C5aR1 antibody comprises a lambda light chain constant region.
  • the light chain constant region comprises (including consisting of or consisting essentially of) the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises an antibody heavy chain variable domain and an antibody light chain variable domain.
  • the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising SYWMN (SEQ ID NO: 1); an HC-CDR2 comprising RIDPX 1 X 2 X 3 X 4 TRYNQKFED (SEQ ID NO: 72), wherein X 1 is G, R, S, or Y, X 2 is D, R, or S, X 3 is G or S, and X 4 is E or G; and an HC-CDR3 comprising FVX 1 PX 2 GX 3 FX 4 Y (SEQ ID NO: 73), wherein X 1 is I or W, X 2 is L, M, Q, S, or V, X 3 is A or G, and X 4 is A or Q; and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising SYWMN (SEQ
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-15, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-31.
  • the anti-C5aR1 antibody comprises a V L comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-44, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-64, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions.
  • the anti-C5aR1 antibody comprises a V L comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-44, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-64.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC- CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-15, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-31, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions; and a V L comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-44, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an LC-CDR2 comprising the amino acid sequence
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-15, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-31; and a V L comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-44, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-64.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of any one of SEQ ID NOs: 76-91; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of the V L comprising the amino acid sequence of any one of SEQ ID NOs: 104- 120.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 76, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 104.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 77, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 105.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 78, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 106.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 79, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 107.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 80, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 106.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 81, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 108.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 82, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 109.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 83, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 110.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 83, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 111.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 84, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 112.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 85, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 113.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 86, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 107.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 87, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 114.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 88, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 115.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 89, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 116.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 90, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 117.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 91, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 118.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 89, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 119.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 89, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 120.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of any one of SEQ ID NOs: 76-91, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of any one of SEQ ID NOs: 104-120, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of any one of SEQ ID NOs: 76-91, and a V L comprising the amino acid sequence of any one of SEQ ID NOs: 104-120.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 76, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 104, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 76 and a V L comprising the amino acid sequence of SEQ ID NO: 104.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 77, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 105, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 77 and a V L comprising the amino acid sequence of SEQ ID NO: 105.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 78, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 106, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 78 and a V L comprising the amino acid sequence of SEQ ID NO: 106.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 79, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 107, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 79 and a V L comprising the amino acid sequence of SEQ ID NO: 107.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 80, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 106, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 80 and a V L comprising the amino acid sequence of SEQ ID NO: 106.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 81, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 108, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 81 and a V L comprising the amino acid sequence of SEQ ID NO: 108.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 82, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 109, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 82 and a V L comprising the amino acid sequence of SEQ ID NO: 109.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 83, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 110, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 83 and a V L comprising the amino acid sequence of SEQ ID NO: 110.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 83, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 111, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 83 and a V L comprising the amino acid sequence of SEQ ID NO: 111.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 84, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 112, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 84 and a V L comprising the amino acid sequence of SEQ ID NO: 112. [00181] In some embodiments, the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 85, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 113, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 85 and a V L comprising the amino acid sequence of SEQ ID NO: 113.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 86, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 107, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 86 and a V L comprising the amino acid sequence of SEQ ID NO: 107.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 87, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 114, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 87 and a V L comprising the amino acid sequence of SEQ ID NO: 114.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 88, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 115, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 88 and a V L comprising the amino acid sequence of SEQ ID NO: 115.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 89, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 116, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 89 and a V L comprising the amino acid sequence of SEQ ID NO: 116.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 90, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 117, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 90 and a V L comprising the amino acid sequence of SEQ ID NO: 117.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 91, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 118, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 91 and a V L comprising the amino acid sequence of SEQ ID NO: 118.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 89, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 119, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 89 and a V L comprising the amino acid sequence of SEQ ID NO: 119.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 89, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 120, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 89 and a V L comprising the amino acid sequence of SEQ ID NO: 120.
  • the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising SGYSWH (SEQ ID NO: 2); an HC-CDR2 comprising YIHSSGDTDYNPSLKR (SEQ ID NO: 16); and an HC-CDR3 comprising SIGDY (SEQ ID NO: 32); and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 45); an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising SQSTHVPW
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32.
  • the anti-C5aR1 antibody comprises a V L comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions.
  • the anti-C5aR1 antibody comprises a V L comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC- CDR2 comprising the amino acid sequence of SEQ ID NO: 16, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions; and a V L comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof comprising up to
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32; and a V L comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of any one of SEQ ID NOs: 92-96; and a V L comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of the V L comprising the amino acid sequence of any one of SEQ ID NOs: 121- 127.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 92, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 121.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 93, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 122.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 93, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 123.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 93, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 124.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 94, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 125.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 95, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 126.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 96, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 127.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 96, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 124.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 96, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 125.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 96, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 126.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of any one of SEQ ID NOs: 92-96, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of any one of SEQ ID NOs: 121-127, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of any one of SEQ ID NOs: 92-96, and a V L comprising the amino acid sequence of any one of SEQ ID NOs: 121-127.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 92, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 121, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 92 and a V L comprising the amino acid sequence of SEQ ID NO: 121.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 122, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 93 and a V L comprising the amino acid sequence of SEQ ID NO: 122.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 123, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 93 and a V L comprising the amino acid sequence of SEQ ID NO: 123.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 124, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 93 and a V L comprising the amino acid sequence of SEQ ID NO: 124.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 94, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 125, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 94 and a V L comprising the amino acid sequence of SEQ ID NO: 125.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 95, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 126, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 95 and a V L comprising the amino acid sequence of SEQ ID NO: 126.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 127, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 96 and a V L comprising the amino acid sequence of SEQ ID NO: 127.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 124, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 96 and a V L comprising the amino acid sequence of SEQ ID NO: 124.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 125, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 96 and a V L comprising the amino acid sequence of SEQ ID NO: 125.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 126, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 96 and a V L comprising the amino acid sequence of SEQ ID NO: 126.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 97, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 128.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 97, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 128, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 97 and a V L comprising the amino acid sequence of SEQ ID NO: 128.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66, or a variant thereof comprising up to about 5 amino acid substitutions in the
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 98, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 129.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 98, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 129, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 98 and a V L comprising the amino acid sequence of SEQ ID NO: 129.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 99, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 130.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 99, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 130, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 99 and a V L comprising the amino acid sequence of SEQ ID NO: 130.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 100, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 131.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 100, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 131, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 100 and a V L comprising the amino acid sequence of SEQ ID NO: 131.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 48, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68, or a variant thereof comprising up to about 5 amino acid substitutions in the
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 48, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 101, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 132.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 101, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 132, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 101 and a V L comprising the amino acid sequence of SEQ ID NO: 132.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69, or a variant thereof comprising up to about 5 amino acid substitutions in the
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 102, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 133.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 102, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 133, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 102 and a V L comprising the amino acid sequence of SEQ ID NO: 133.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 50, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70, or a variant thereof comprising up to about 5 amino acid substitutions in the
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 50, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 103, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 134.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 134, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 103 and a V L comprising the amino acid sequence of SEQ ID NO: 134.
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71, or a variant thereof comprising up to about 5 amino acid substitutions in
  • the anti-C5aR1 antibody comprises a V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71.
  • the anti-C5aR1 antibody comprises a V H comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the V H comprising the amino acid sequence of SEQ ID NO: 102, and a V L comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the V L comprising the amino acid sequence of SEQ ID NO: 135.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 102, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a V L comprising the amino acid sequence of SEQ ID NO: 135, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-C5aR1 antibody comprises a V H comprising the amino acid sequence of SEQ ID NO: 102 and a V L comprising the amino acid sequence of SEQ ID NO: 135.
  • the amino acid substitutions described above are limited to "exemplary substitutions” shown in Table 4 of this application. In some embodiments, the amino acid substitutions are limited to “preferred substitutions” shown in Table 4 of this application.
  • functional epitopes can be mapped by combinatorial alanine scanning. In this process, a combinatorial alanine-scanning strategy can be used to identify amino acids in the C5aR1 protein that are necessary for interaction with C5aR1 antibodies.
  • the epitope is conformational and crystal structure of anti- C5aR1 antibodies bound to C5aR1 may be employed to identify the epitopes.
  • the present application provides antibodies which compete with any one of the C5aR1 antibodies described herein for binding to C5aR1. In some embodiments, the present application provides antibodies which compete with any one of the anti-C5aR1 antibodies provided herein for binding to an epitope on the C5aR1.
  • an anti-C5aR1 antibody that binds to the same epitope as an anti-C5aR1 antibody comprising a V H comprising the amino acid sequence of any one of SEQ ID NOs: 76-103, and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 104-135.
  • an anti-C5aR1 antibody is provided that specifically binds to C5aR1 competitively with an anti-C5aR1 antibody comprising a V H comprising the amino acid sequence of any one of SEQ ID NOs: 76-103 and a V L comprising the amino acid sequence of any one of SEQ ID NOs: 104-135.
  • competition assays may be used to identify a monoclonal antibody that competes with an anti-C5aR1 antibody described herein for binding to C5aR1.
  • Competition assays can be used to determine whether two antibodies bind to the same epitope by recognizing identical or sterically overlapping epitopes or one antibody competitively inhibits binding of another antibody to the antigen. In certain embodiments, such a competing antibody binds to the same epitope that is bound by an antibody described herein.
  • Exemplary competition assays include, but are not limited to, routine assays such as those provided in Harlow and Lane (1988) Antibodies: A Laboratory Manual ch.14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.).
  • Anti-C5aR1 antibodies comprising CDRs, V H and/or V L sequences from antibodies described herein, but based on prediction algorithms other than those exemplified in the tables below, are within the scope of this invention.
  • Table 2A Exemplary anti-C5aR1 antibody CDR sequences.
  • Table 2B Exemplary anti-C5aR1 antibody CDR sequences.
  • Table 2C Exemplary anti-C5aR1 antibody CDR sequences.
  • the complement system consists of a tightly regulated network of proteins that play an important role in host defense and inflammation. Complement activation is known to occur through three different pathways: alternate, classical and lectin pathways involving proteins that mostly exist as inactive zymogens that are then sequentially cleaved and activated. All the complement pathways converge at C3 which is the most abundant complement protein found in blood, resulting in the formation of the activation products, C3a, C3b, C5a and the membrane attack complex (C5b-9).
  • C5a anaphylatoxin chemotactic receptor 1 (C5aR1) is one of the two high affinity receptors for the ligand, C5a. It has been reported that the second and third extracellular loops (ECLs) of C5aR1 were essential for ligand binding (Pease et al.1994.).
  • C5aR1 is a member of GPCR and couples to a wide range of G proteins such as G ⁇ i2 (Sheth et al.1991; Skokowa et al.,2005) which is a pertussis toxin (PT)-sensitive G protein, and G ⁇ 16, a PT-insensitive G protein (Monk and Partridge, 1993).
  • Activated C5aR1 has also been shown to associate with two of the four mammalian ⁇ -arrestins ( ⁇ -arrestin 1, 2) which have different dependencies on the phosphorylation status of the receptor (Braun et al., 2003).
  • the human C5aR1 binds C5a with a Kd of 1nM but has an affinity for C5a desArg that is 10- 100 folds lower.
  • C5a has a short half-life in serum as the C-terminal arginine is quickly cleaved by carboxypeptidase N to form C5a desArg, which binds to C5aR1 with reduced affinity and displays biased signaling.
  • C5a desArg unlike C5a, does not signal the G ⁇ pathway and does not stimulate granulocyte release. However, C5a desArg does stimulate neutrophil chemotaxis, so it is interest to also block C5a desArg binding to prevent neutrophil migration to the site of inflammation (Eric Wagner et al., Nature Rev, 2010).
  • C5aR1 has been found to be expressed on various inflammatory cells and smooth muscle cells to promote an inflammatory reaction. It is also present on subsets of T cells and dendritic cells to regulate the adaptive immune response (Kemper et al. Nature Rev. Immunol.7.9-18, 2007). C5a-C5aR interaction is required for the optimal oxidative burst and phagocytosis, which form the fundamental machinery in innate immunity for bacterial clearance. The binding of C5a ligand and its receptor C5aR thereof induces an inflammatory reaction by inducing cytokine and chemokine expression (Monsinjon et al. FASEB J 17:1003–1014, 2003.; Fukuoka et al.
  • C5a-C5aR interaction is also an essential step in neutrophil migration by causing adhesion molecule expression and inducing chemokine production (Riedemann et al. Immunity 19:193–202, 2003.). It has been reported that C5aR1 and its ligand C5a play a key role in initiating and maintaining several inflammatory responses by recruiting and activating neutrophils and monocytes in the lungs (Julien Carvelli et al. Nature 588, 146-150, 2020). In addition, C5a perturbs coagulation and fibrinolysis pathway, resulting in damaging intravascular coagulation (Muhlfelder et al.
  • C5aR and C3aR agonists increased proliferation, migration and invasion of ovarian cancer cells
  • C5aR and C3aR antagonists decreased proliferation of these cells.
  • Anaphylatoxin receptors signal through the PI3/AKT pathway in cancer cells, and the proliferative effect of C5aR and C3aR stimulation could be eliminated by AKT silencing (Cho Ms et al., Cell Rep, 2014).
  • C5a [00262]
  • the ligand C5a is an activated product of the complement system, and elicits the broadest immune responses. C5a is produced in serum as one of the core effector components of the complement response and is one of best described and most potent proinflammatory mediators derived from the complement systems.
  • C5a anaphylatoxin chemotactic receptor 1 (C5aR1, also known as CD88)
  • CD88 G-protein- coupled receptor
  • C5a ligand and its receptor C5aR thereof induces an inflammatory reaction by inducing cytokine and chemokine expression (Monsinjon et al. FASEB J 17:1003–1014, 2003.; Fukuoka et al. Clin Exp Immunol 131:248–253, 2003).
  • the other receptor, G protein-coupled receptor 77 (GPR77, also known as C5L2) recognized C5a and its inactivated form, C5a desArg, but seems to downregulate rather than promote an inflammary responses (Monk et al. Br, J. Pharmacol, 152,429-448, 2007).
  • C5a has been shown to be spasmogenic, chemotactic to increase vascular permeability and induce the release pharmacologically active mediators from numerous cell types. It has also been shown to directly or indirectly induce cytokine release from macrophages and to augment humoral- and cell-mediated immune responses in vitro (Shin et al., Science 162:361, 1968; Schorlemmer, et al., Nature 261:48, 1976.).
  • Full-length anti-C5aR1 antibody [00263]
  • the anti-C5aR1 antibody in some embodiments is a full-length anti-C5aR1 antibody.
  • the full-length anti-C5aR1 antibody is an IgA, IgD, IgE, IgG, or IgM. In some embodiments, the full-length anti-C5aR1 antibody comprises IgG constant domains, such as constant domains of any one of IgG1, IgG2, IgG3, and IgG4 including variants thereof. In some embodiments, the full-length anti-C5aR1 antibody comprises a lambda light chain constant region. In some embodiments, the full-length anti- C5aR1 antibody comprises a kappa light chain constant region. In some embodiments, the full-length anti-C5aR1 antibody is a full-length human anti-C5aR1 antibody.
  • the full-length anti-C5aR1 antibody comprises an Fc sequence of a mouse immunoglobulin. In some embodiments, the full-length anti-C5aR1 antibody comprises an Fc sequence that has been altered or otherwise changed so that it has enhanced antibody dependent cellular cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC) effector function.
  • ADCC antibody dependent cellular cytotoxicity
  • CDC complement dependent cytotoxicity
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG2 constant domains, wherein the anti-C5aR1 antibody specifically binds to C5aR1.
  • the IgG2 is human IgG2.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the IgG3 is human IgG3.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00267] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody specifically binds to C5aR1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs:
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38, or a variant thereof comprising up to about 3
  • the IgG2 is human IgG2.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG3 constant domains
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39
  • the IgG3 is human IgG3.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs:
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38, or a variant thereof comprising up to about 5 (such as about any of 1, 2, 3, 4, or 5) amino acid substitutions in the HC-CDR sequences; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38, or a variant thereof comprising up to about 5 (such as about any of 1, 2, 3, 4, or 5) amino acid substitutions in the HC-CDR sequences; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-51, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 52-57
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-51, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 52-57,
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 28; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 30; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 32; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 36; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 48, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 38; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 50, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 28; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 30; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 32; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 36; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 48, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 38; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 50, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 76- 103, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a light chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 104-135, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 76- 103, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a light chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 104-135, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the IgG2 is human IgG2.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG3 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 76- 103, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity
  • a light chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 104-135, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the IgG3 is human IgG3.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 76- 103, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity
  • a light chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 104-135, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 76- 103, and a light chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 104-135.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 76- 103, and a light chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 104-135.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00326] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 76 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 104.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 77 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 105.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00328] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 78 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 106.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 79 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 107.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00330] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 80 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 106.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 81 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 108.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00332] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 82 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 109.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 83 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 110.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00334] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 83 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 111.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 84 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 112.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00336] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 85 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 113.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 86 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 107.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00338] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 87 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 114.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 88 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 115.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00340] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 89 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 116.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 90 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 117.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00342] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 91 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 118.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 89 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 119.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00344] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 89 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 120.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 92 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 121.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00346] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 93 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 122.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 93 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 123.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00348] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 93 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 124.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 94 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 125.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00350] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 95 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 126.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 127.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00352] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 124.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 125.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00354] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 126.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 97 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 128.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00356] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 98 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 129.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 99 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 130.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00358] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 100 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 131.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 101 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 132.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00360] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 102 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 133.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG1 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 103 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 134.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00362] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 102 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 135.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 76 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 104.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00364] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 77 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 105.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 78 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 106.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00366] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 79 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 107.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 80 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 106.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00368] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 81 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 108.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 82 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 109.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00370] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 83 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 110.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 83 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 111.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00372] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 84 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 112.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 85 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 113.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00374] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 86 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 107.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 87 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 114.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00376] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 88 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 115.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 89 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 116.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00378] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 90 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 117.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 91 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 118.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00380] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 89 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 119.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 89 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 120.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00382] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 92 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 121.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 93 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 122.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00384] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 93 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 123.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 93 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 124.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00386] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 94 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 125.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 95 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 126.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00388] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 127.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 124.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00390] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 125.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 126.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00392] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 97 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 128.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 98 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 129.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00394] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 99 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 130.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 100 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 131.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00396] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 101 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 132.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 102 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 133.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00398] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 103 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 134.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a full-length anti-C5aR1 antibody comprising IgG4 constant domains
  • the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 102 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 135.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • Binding affinity can be indicated by Kd, Koff, Kon, or Ka. The term "Koff”, as used herein, is intended to refer to the off-rate constant for dissociation of an antibody from the antibody /antigen complex, as determined from a kinetic selection set up.
  • Kd dissociation constant of a particular antibody- antigen interaction, and describes the concentration of antigen required to occupy one half of all of the antibody-binding domains present in a solution of antibody molecules at equilibrium, and is equal to Koff/Kon.
  • the measurement of Kd presupposes that all binding agents are in solution.
  • the corresponding equilibrium rate constant is expressed as EC50, which gives a good approximation of Kd.
  • the affinity constant, Ka is the inverse of the dissociation constant, Kd.
  • the dissociation constant (Kd) is used as an indicator showing affinity of antibody moieties to antigens. For example, easy analysis is possible by the Scatchard method using antibodies marked with a variety of marker agents, as well as by using Biacore (made by Amersham Biosciences), analysis of biomolecular interactions by surface plasmon resonance, according to the user's manual and attached kit.
  • the Kd value that can be derived using these methods is expressed in units of M.
  • An antibody that specifically binds to a target may have a Kd of, for example, ⁇ 10 -7 M, ⁇ 10 -8 M, ⁇ 10 -9 M, ⁇ 10 -10 M, ⁇ 10 -11 M, ⁇ 10 -12 M, or ⁇ 10 -13 M.
  • Binding specificity of the antibody can be determined experimentally by methods known in the art. Such methods comprise, but are not limited to, Western blots, ELISA-, RIA-, ECL-, IRMA-, EIA-, BIAcore-tests and peptide scans.
  • the anti-C5aR1 antibody specifically binds to a target C5aR1 with a Kd of about 10 -7 M to about 10 -13 M (such as about 10 -7 M to about 10 -13 M, about 10 -8 M to about 10 -13 M, about 10 -9 M to about 10 -13 M, or about 10 -10 M to about 10 -12 M).
  • the Kd of the binding between the anti-C5aR1 antibody and C5aR1 is about 10 -7 M to about 10 -13 M, about 1 ⁇ 10 -7 M to about 5 ⁇ 10 -13 M, about 10 -7 M to about 10 -12 M, about 10 -7 M to about 10 -11 M, about 10 -7 M to about 10 -10 M, about 10 -7 M to about 10 -9 M, about 10 -8 M to about 10 -13 M, about 1 ⁇ 10 -8 M to about 5 ⁇ 10 -13 M, about 10- 8 M to about 10 -12 M, about 10 -8 M to about 10 -11 M, about 10 -8 M to about 10 -10 M, about 10- 8 M to about 10 -9 M, about 5 ⁇ 10 -9 M to about 1 ⁇ 10 -13 M, about 5 ⁇ 10 -9 M to about 1 ⁇ 10 -12 M, about 5 ⁇ 10 -9 M to about 1 ⁇ 10 -11 M, about 5 ⁇ 10 -9 M to about 1 ⁇ 10 -10 M, about 10 -9 M to about 10 -13 M,
  • the Kd of the binding between the anti-C5aR1 antibody and a C5aR1 is about 10 -7 M to about 10 -13 M.
  • the Kd of the binding between the anti-C5aR1 antibody and a non-target is more than the Kd of the binding between the anti-C5aR1 antibody and the target, and is herein referred to in some embodiments as the binding affinity, of the anti- C5aR1 antibody to the target (e.g., C5aR1) is higher than that to a non-target.
  • the non-target is an antigen that is not C5aR1.
  • the Kd of the binding between the anti-C5aR1 antibody (against C5aR1) and a non-C5aR1 target can be at least about 10 times, such as about 10-100 times, about 100-1000 times, about 10 3 -10 4 times, about 10 4 -10 5 times, about 10 5 -10 6 times, about 10 6 -10 7 times, about 10 7 -10 8 times, about 10 8 -10 9 times, about 10 9 -10 10 times, about 10 10 -10 11 times, or about 10 11 -10 12 times of the Kd of the binding between the anti-C5aR1 antibody and a target C5aR1.
  • the anti-C5aR1 antibody binds to a non-target with a Kd of about 10 -1 M to about 10 -6 M (such as about 10 -1 M to about 10 -6 M, about 10 -1 M to about 10 -5 M, or about 10 -2 M to about 10 -4 M).
  • the non-target is an antigen that is not C5aR1.
  • the Kd of the binding between the anti-C5aR1 antibody and a non-C5aR1 target is about 10 -1 M to about 10 -6 M, about 1 ⁇ 10 -1 M to about 5 ⁇ 10 -6 M, about 10 -1 M to about 10 -5 M, about 1 ⁇ 10 -1 M to about 5 ⁇ 10 -5 M, about 10 -1 M to about 10 -4 M, about 1 ⁇ 10 -1 M to about 5 ⁇ 10 -4 M, about 10 -1 M to about 10 -3 M, about 1 ⁇ 10 -1 M to about 5 ⁇ 10 -3 M, about 10 -1 M to about 10 -2 M, about 10 -2 M to about 10 -6 M, about 1 ⁇ 10 -2 M to about 5 ⁇ 10 -6 M, about 10 -2 M to about 10 -5 M, about 1 ⁇ 10 -2 M to about 5 ⁇ 10 -5 M, about 10 -2 M to about 10 -4 M, about 1 ⁇ 10 -2 M to about 5 ⁇ 10 -4 M, about 10 -2 M to about 10 -3 M, about
  • the anti-C5aR1 antibody when referring to that the anti-C5aR1 antibody specifically recognizes a target C5aR1 at a high binding affinity, and binds to a non-target at a low binding affinity, the anti-C5aR1 antibody will bind to the target C5aR1 with a Kd of about 10 -7 M to about 10 -13 M (such as about 10 -7 M to about 10 -13 M, about 10 -8 M to about 10 -13 M, about 10 -9 M to about 10 -13 M, or about 10 -10 M to about 10 -12 M), and will bind to the non-target with a Kd of about 10 -1 M to about 10 -6 M (such as about 10 -1 M to about 10 -6 M, about 10 -1 M to about 10 -5 M, or about 10 -3 M to about 10 -4 M).
  • a Kd of about 10 -7 M to about 10 -13 M such as about 10 -7 M to about 10 -13 M, about 10 -8 M to about 10
  • the binding affinity of the anti-C5aR1 antibody is compared to that of a control anti-C5aR1 antibody (such as avdoralimab).
  • the Kd of the binding between the control anti-C5aR1 antibody and C5aR1 can be at least about 2 times, such as about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, about 9 times, about 10 times, about 10-100 times, about 100-1000 times, about 10 3 -10 4 times of the Kd of the binding between the anti-C5aR1 antibody described herein and C5aR1.
  • Nucleic acid molecules encoding the anti-C5aR1 antibodies are also contemplated.
  • a nucleic acid (or a set of nucleic acids) encoding a full-length anti-C5aR1 antibody including any of the full-length anti- C5aR1 antibodies described herein.
  • the nucleic acid (or a set of nucleic acids) encoding the anti-C5aR1 antibody described herein may further comprises a nucleic acid sequence encoding a peptide tag (such as protein purification tag, e.g., His-tag, HA tag).
  • isolated host cells comprising an anti-C5aR1 antibody, an isolated nucleic acid encoding the polypeptide components of the anti-C5aR1 antibody, or a vector comprising a nucleic acid encoding the polypeptide components of the anti-C5aR1 antibody described herein.
  • the present application also includes variants to these nucleic acid sequences.
  • the variants include nucleotide sequences that hybridize to the nucleic acid sequences encoding the anti-C5aR1 antibodies of the present application under at least moderately stringent hybridization conditions.
  • the present application also provides vectors in which a nucleic acid of the present application is inserted.
  • an anti-C5aR1 antibody e.g., full-length anti-C5aR1 antibody
  • a natural or synthetic nucleic acid encoding the anti-C5aR1 antibody can be achieved by inserting the nucleic acid into an appropriate expression vector, such that the nucleic acid is operably linked to 5' and 3' regulatory elements, including for example a promoter (e.g., a lymphocyte-specific promoter) and a 3' untranslated region (UTR).
  • the vectors can be suitable for replication and integration in eukaryotic host cells.
  • Typical cloning and expression vectors contain transcription and translation terminators, initiation sequences, and promoters useful for regulation of the expression of the desired nucleic acid sequences.
  • the nucleic acids of the present application may also be used for nucleic acid immunization and gene therapy, using standard gene delivery protocols. Methods for gene delivery are known in the art. See, e.g., U.S. Pat. Nos.5,399,346, 5,580,859, 5,589,466, incorporated by reference herein in their entireties. In some embodiments, the application provides a gene therapy vector.
  • the nucleic acid can be cloned into a number of types of vectors.
  • the nucleic acid can be cloned into a vector including, but not limited to a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid.
  • Vectors of particular interest include expression vectors, replication vectors, probe generation vectors, and sequencing vectors.
  • the expression vector may be provided to a cell in the form of a viral vector. Viral vector technology is well known in the art and is described, for example, in Green and Sambrook (2013, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York), and in other virology and molecular biology manuals.
  • Viruses which are useful as vectors include, but are not limited to, retroviruses, adenoviruses, adeno- associated viruses, herpes viruses, and lentiviruses.
  • a suitable vector contains an origin of replication functional in at least one organism, a promoter sequence, convenient restriction endonuclease sites, and one or more selectable markers (see, e.g., WO 01/96584; WO 01/29058; and U.S. Pat. No. 6,326,193).
  • retroviruses provide a convenient platform for gene delivery systems.
  • a selected gene can be inserted into a vector and packaged in retroviral particles using techniques known in the art.
  • the recombinant virus can then be isolated and delivered to cells of the subject either in vivo or ex vivo.
  • retroviral systems are known in the art
  • adenovirus vectors are used.
  • a number of adenovirus vectors are known in the art.
  • lentivirus vectors are used.
  • Vectors derived from retroviruses such as the lentivirus are suitable tools to achieve long-term gene transfer since they allow long-term, stable integration of a transgene and its propagation in daughter cells.
  • Lentiviral vectors have the added advantage over vectors derived from onco-retroviruses such as murine leukemia viruses in that they can transduce non-proliferating cells, such as hepatocytes. They also have the added advantage of low immunogenicity.
  • Additional promoter elements e.g., enhancers, regulate the frequency of transcriptional initiation.
  • these are located in the region 30-110 bp upstream of the start site, although a number of promoters have recently been shown to contain functional elements downstream of the start site as well.
  • the spacing between promoter elements frequently is flexible, so that promoter function is preserved when elements are inverted or moved relative to one another.
  • tk thymidine kinase
  • a suitable promoter is the immediate early cytomegalovirus (CMV) promoter sequence.
  • CMV immediate early cytomegalovirus
  • This promoter sequence is a strong constitutive promoter sequence capable of driving high levels of expression of any polynucleotide sequence operatively linked thereto.
  • Another example of a suitable promoter is Elongation Factor-1 ⁇ (EF-1 ⁇ ).
  • constitutive promoter sequences may also be used, including, but not limited to the simian virus 40 (SV40) early promoter, mouse mammary tumor virus (MMTV), human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus promoter, as well as human gene promoters such as, but not limited to, the actin promoter, the myosin promoter, the hemoglobin promoter, and the creatine kinase promoter. Further, the application should not be limited to the use of constitutive promoters.
  • inducible promoters are also contemplated as part of the application.
  • the use of an inducible promoter provides a molecular switch capable of turning on expression of the polynucleotide sequence to which it is operatively linked when such expression is desired, or turning off the expression when expression is not desired.
  • inducible promoters include, but are not limited to a metallothionine promoter, a glucocorticoid promoter, a progesterone promoter, and a tetracycline promoter.
  • the expression of the anti-C5aR1 antibody is inducible.
  • a nucleic acid sequence encoding the anti-C5aR1 antibody is operably linked to an inducible promoter, including any inducible promoter described herein.
  • inducible promoters include any inducible promoter described herein.
  • the use of an inducible promoter provides a molecular switch capable of turning on expression of the polynucleotide sequence to which it is operatively linked when such expression is desired, or turning off the expression when expression is not desired.
  • Exemplary inducible promoter systems for use in eukaryotic cells include, but are not limited to, hormone-regulated elements (e.g., see Mader, S. and White, J. H. (1993) Proc. Natl. Acad. Sci.
  • the inducible promoter system for use to express the anti-C5aR1 antibody is the Tet system. In some embodiments, the inducible promoter system for use to express the anti-C5aR1 antibody is the lac repressor system from E. coli.
  • An exemplary inducible promoter system for use in the present application is the Tet system. Such systems are based on the Tet system described by Gossen et al. (1993).
  • a polynucleotide of interest is under the control of a promoter that comprises one or more Tet operator (TetO) sites.
  • Tet repressor In the inactive state, Tet repressor (TetR) will bind to the TetO sites and repress transcription from the promoter.
  • TetR Tet repressor
  • the active state e.g., in the presence of an inducing agent such as tetracycline (Tc), anhydrotetracycline, doxycycline (Dox), or an active analog thereof, the inducing agent causes release of TetR from TetO, thereby allowing transcription to take place.
  • an inducing agent such as tetracycline (Tc), anhydrotetracycline, doxycycline (Dox), or an active analog thereof.
  • Doxycycline is a member of the tetracycline family of antibiotics having the chemical name of 1-dimethylamino-2,4a,5,7,12- pentahydroxy-11-methyl-4,6-dioxo-1,4a,11,11a,12,12a-hexahydrotetracene-3-carboxamide.
  • a TetR is codon-optimized for expression in mammalian cells, e.g., murine or human cells.
  • Codon bias i.e., bias for use of a particular codon(s) for a given amino acid. Codon bias often correlates with the presence of a predominant species of tRNA for a particular codon, which in turn increases efficiency of mRNA translation.
  • a coding sequence derived from a particular organism may be tailored for improved expression in a different organism (e.g., a eukaryote) through codon optimization.
  • a particular organism e.g., a prokaryote
  • a different organism e.g., a eukaryote
  • Tet-Off transcription is inactive in the presence of Tc or Dox.
  • a tetracycline-controlled transactivator protein which is composed of TetR fused to the strong transactivating domain of VP16 from Herpes simplex virus, regulates expression of a target nucleic acid that is under transcriptional control of a tetracycline-responsive promoter element (TRE).
  • the TRE is made up of TetO sequence concatamers fused to a promoter (commonly the minimal promoter sequence derived from the human cytomegalovirus (hCMV) immediate-early promoter).
  • hCMV human cytomegalovirus
  • tTA In the presence of Tc or Dox, tTA cannot bind to the TRE, and expression from the target gene remains inactive. [00424] Conversely, in the Tet-On system, transcription is active in the presence of Tc or Dox.
  • the Tet-On system is based on a reverse tetracycline-controlled transactivator, rtTA. Like tTA, rtTA is a fusion protein comprised of the TetR repressor and the VP16 transactivation domain. However, a four amino acid change in the TetR DNA binding moiety alters rtTA's binding characteristics such that it can only recognize the tetO sequences in the TRE of the target transgene in the presence of Dox.
  • transcription of the TRE-regulated target gene is stimulated by rtTA only in the presence of Dox.
  • Another inducible promoter system is the lac repressor system from E. coli (See Brown et al., Cell 49:603-612 (1987)).
  • the lac repressor system functions by regulating transcription of a polynucleotide of interest operably linked to a promoter comprising the lac operator (lacO).
  • lacO lac operator
  • lacR lac repressor
  • lacR lac binds to LacO, thus preventing transcription of the polynucleotide of interest.
  • the expression vector to be introduced into a cell can also contain either a selectable marker gene or a reporter gene or both to facilitate identification and selection of expressing cells from the population of cells sought to be transfected or infected through viral vectors.
  • the selectable marker may be carried on a separate piece of DNA and used in a co- transfection procedure. Both selectable markers and reporter genes may be flanked with appropriate regulatory sequences to enable expression in the host cells.
  • reporter genes are used for identifying potentially transfected cells and for evaluating the functionality of regulatory sequences.
  • a reporter gene is a gene that is not present in or expressed by the recipient organism or tissue and that encodes a polypeptide whose expression is manifested by some easily detectable property, e.g., enzymatic activity. Expression of the reporter gene is assayed at a suitable time after the DNA has been introduced into the recipient cells.
  • Suitable reporter genes may include genes encoding luciferase, ⁇ -galactosidase, chloramphenicol acetyl transferase, secreted alkaline phosphatase, or the green fluorescent protein gene (e.g., Ui-Tel et al., 2000 FEBS Letters 479: 79-82).
  • Suitable expression systems are well known and may be prepared using known techniques or obtained commercially.
  • the construct with the minimal 5' flanking region showing the highest level of expression of reporter gene is identified as the promoter.
  • Such promoter regions may be linked to a reporter gene and used to evaluate agents for the ability to modulate promoter-driven transcription.
  • nucleic acid encoding a full-length anti-C5aR1 antibody according to any of the full-length anti-C5aR1 antibodies described herein.
  • the nucleic acid comprises one or more nucleic acid sequences encoding the heavy and light chains of the full-length anti-C5aR1 antibody.
  • each of the one or more nucleic acid sequences are contained in separate vectors.
  • at least some of the nucleic acid sequences are contained in the same vector.
  • all of the nucleic acid sequences are contained in the same vector.
  • Vectors may be selected, for example, from the group consisting of mammalian expression vectors and viral vectors (such as those derived from retroviruses, adenoviruses, adeno-associated viruses, herpes viruses, and lentiviruses).
  • viral vectors such as those derived from retroviruses, adenoviruses, adeno-associated viruses, herpes viruses, and lentiviruses.
  • Physical methods for introducing a polynucleotide into a host cell include calcium phosphate precipitation, lipofection, particle bombardment, microinjection, electroporation, and the like. Methods for producing cells comprising vectors and/or exogenous nucleic acids are well-known in the art. See, for example, Green and Sambrook (2013, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York). In some embodiments, the introduction of a polynucleotide into a host cell is carried out by calcium phosphate transfection. [00431] Biological methods for introducing a polynucleotide of interest into a host cell include the use of DNA and RNA vectors.
  • Viral vectors and especially retroviral vectors, have become the most widely used method of inserting genes into mammalian, e.g., human cells.
  • Other viral vectors can be derived from lentivirus, poxviruses, herpes simplex virus 1, adenoviruses and adeno-associated viruses, and the like. See, for example, U.S. Pat. Nos. 5,350,674 and 5,585,362.
  • Chemical means for introducing a polynucleotide into a host cell include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes.
  • An exemplary colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (e.g., an artificial membrane vesicle).
  • an exemplary delivery vehicle is a liposome.
  • the nucleic acid may be associated with a lipid.
  • the nucleic acid associated with a lipid may be encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the oligonucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid.
  • Lipid, lipid/DNA or lipid/expression vector associated compositions are not limited to any particular structure in solution. For example, they may be present in a bilayer structure, as micelles, or with a "collapsed" structure. They may also simply be interspersed in a solution, possibly forming aggregates that are not uniform in size or shape.
  • Lipids are fatty substances which may be naturally occurring or synthetic lipids.
  • lipids include the fatty droplets that naturally occur in the cytoplasm as well as the class of compounds which contain long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, amino alcohols, and aldehydes.
  • assays include, for example, "molecular biological” assays well known to those of skill in the art, such as Southern and Northern blotting, RT-PCR and PCR; "biochemical” assays, such as detecting the presence or absence of a particular peptide, e.g., by immunological means (ELISAs and Western blots) or by assays described herein to identify agents falling within the scope of the application.
  • molecular biological assays well known to those of skill in the art, such as Southern and Northern blotting, RT-PCR and PCR
  • biochemical assays, such as detecting the presence or absence of a particular peptide, e.g., by immunological means (ELISAs and Western blots) or by assays described herein to identify agents falling within the scope of the application.
  • the anti-C5aR1 antibody is a monoclonal antibody or derived from a monoclonal antibody.
  • the anti-C5aR1 antibody comprises V H and V L domains, or variants thereof, from the monoclonal antibody.
  • the anti-C5aR1 antibody further comprises C H 1 and C L domains, or variants thereof, from the monoclonal antibody.
  • Monoclonal antibodies can be prepared, e.g., using known methods in the art, including hybridoma methods, phage display methods, or using recombinant DNA methods. Additionally, exemplary phage display methods are described herein and in the Examples below.
  • a hamster, mouse, or other appropriate host animal is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent.
  • the lymphocytes can be immunized in vitro.
  • the immunizing agent can include a polypeptide or a fusion protein of the protein of interest.
  • PBLs peripheral blood lymphocytes
  • spleen cells or lymph node cells are used if non-human mammalian sources are desired.
  • the lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell.
  • a suitable fusing agent such as polyethylene glycol
  • Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine, and human origin. Usually, rat or mouse myeloma cell lines are employed.
  • the hybridoma cells can be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells.
  • the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT medium”), which prevents the growth of HGPRT-deficient cells.
  • HAT medium hypoxanthine, aminopterin, and thymidine
  • the immortalized cell lines fuse efficiently, support stable high-level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium.
  • the immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, California and the American Type Culture Collection, Manassas, Virginia.
  • the culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the polypeptide.
  • the binding specificity of monoclonal antibodies produced by the hybridoma cells can be determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). Such techniques and assays are known in the art.
  • the binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal.
  • the clones can be sub-cloned by limiting dilution procedures and grown by standard methods. Goding, supra. Suitable culture media for this purpose include, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal.
  • the monoclonal antibodies secreted by the sub-clones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.
  • the anti-C5aR1 antibody comprises sequences from a clone selected from an antibody library (such as a phage library presenting scFv or Fab fragments). The clone may be identified by screening combinatorial libraries for antibody fragments with the desired activity or activities.
  • repertoires of V H and V L genes are separately cloned by polymerase chain reaction (PCR) and recombined randomly in phage libraries, which can then be screened for antigen-binding phage as described in Winter et al., Ann. Rev. Immunol., 12: 433-455 (1994).
  • Phage typically display antibody fragments, either as scFv fragments or as Fab fragments. Libraries from immunized sources provide high- affinity antibodies to the immunogen without the requirement of constructing hybridomas.
  • naive repertoire can be cloned (e.g., from human) to provide a single source of antibodies to a wide range of non-self and also self-antigens without any immunization as described by Griffiths et al., EMBO J, 12: 725-734 (1993).
  • naive libraries can also be made synthetically by cloning unrearranged V-gene segments from stem cells, and using PCR primers containing random sequence to encode the highly variable CDR3 regions and to accomplish rearrangement in vitro, as described by Hoogenboom and Winter, J. Mol. Biol., 227: 381-388 (1992).
  • Patent publications describing human antibody phage libraries include, for example: U.S. Pat.
  • the anti-C5aR1 antibodies can be prepared using phage display to screen libraries for anti-C5aR1 antibody moieties specific to the target C5aR1.
  • the library can be a human scFv phage display library having a diversity of at least 1 ⁇ 10 9 (such as at least about any of 1 ⁇ 10 9 , 2.5 ⁇ 10 9 , 5 ⁇ 10 9 , 7.5 ⁇ 10 9 , 1 ⁇ 10 10 , 2.5 ⁇ 10 10 , 5 ⁇ 10 10 , 7.5 ⁇ 10 10 , or 1 ⁇ 10 11 ) unique human antibody fragments.
  • the library is a na ⁇ ve human library constructed from DNA extracted from human PMBCs and spleens from healthy donors, encompassing all human heavy and light chain subfamilies.
  • the library is a na ⁇ ve human library constructed from DNA extracted from PBMCs isolated from patients with various diseases, such as patients with autoimmune diseases, cancer patients, and patients with infectious diseases.
  • the library is a semi- synthetic human library, wherein heavy chain CDR3 is completely randomized, with all amino acids (with the exception of cysteine) equally likely to be present at any given position (see, e.g., Hoet, R.M. et al., Nat. Biotechnol.23(3):344-348, 2005).
  • the heavy chain CDR3 of the semi-synthetic human library has a length from about 5 to about 24 (such as about any of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24) amino acids.
  • the library is a fully-synthetic phage display library.
  • the library is a non-human phage display library.
  • Phage clones that bind to the target C5aR1 with high affinity can be selected by iterative binding of phage to the target C5aR1, which is bound to a solid support (such as, for example, beads for solution panning or mammalian cells for cell panning), followed by removal of non-bound phage and by elution of specifically bound phage. The bound phage clones are then eluted and used to infect an appropriate host cell, such as E. coli XL1-Blue, for expression and purification.
  • a solid support such as, for example, beads for solution panning or mammalian cells for cell panning
  • the panning can be performed for multiple (such as about any of 2, 3, 4, 5, 6 or more) rounds with solution panning, cell panning, or a combination of both, to enrich for phage clones binding specifically to the target C5aR1.
  • Enriched phage clones can be tested for specific binding to the target C5aR1 by any methods known in the art, including for example ELISA and FACS.
  • An alternative method for screening antibody libraries is to display the protein on the surface of yeast cells. Wittrup et al. (US Patent Nos.6,699,658 and 6,696,251) have developed a method for a yeast cell display library.
  • a component involves the yeast agglutinin protein (Aga1), which is anchored to the yeast cell wall.
  • Another component involves a second subunit of the agglutinin protein Aga2, which can display on the surface yeast cells through disulfide bonds to Aga1 protein.
  • the protein Aga1 is expressed from a yeast chromosome after the Aga1 gene integration.
  • a library of single chain variable fragments (scFv) is fused genetically to Aga2 sequence in the yeast display plasmid, which, after transformation, is maintained in yeast episomally with a nutritional marker. Both of the Aga1 and Aga2 proteins were expressed under the control of the galactose-inducible promoter.
  • V H and V K fragments Human antibody V gene repertoire (V H and V K fragments) are obtained by PCR method using a pool of degenerate primers (Sblattero, D. & Bradbury, A. Immunotechnology 3, 271-2781998).
  • the PCR templates are from the commercially available RNAs or cDNAs, including PBMC, spleen, lymph nodes, bone marrow and tonsils. Separate V H and VK PCR libraries were combined, then assembled together in the scFv format by overlap extension PCR ( Sheets, M.D. et al., Proc. Natl. Acad. Sci. USA 95, 6157- 6162 1998.).
  • the resultant scFv PCR products are cloned into the yeast display plasmid in the yeasts by homologous recombination.
  • the anti-C5aR1 antibodies can be discovered using mammalian cell display systems in which antibody moieties are displayed on the cell surface and those specific to the target C5aR1 are isolated by the antigen-guided screening method, as described in U.S. patent No.7,732,195B2.
  • a Chinese hamster ovary (CHO) cell library representing a large set of human IgG antibody genes can be established and used to discover the clones expressing high-affinity antibody genes.
  • Another display system has been developed to enable simultaneous high-level cell surface display and secretion of the same protein through alternate splicing, where the displayed protein phenotype remains linked to genotype, allowing soluble secreted antibody to be simultaneously characterized in biophysical and cell-based functional assays.
  • This approach overcomes many limitations of previous mammalian cell display, enabling direct selection and maturation of antibodies in the form of full-length, glycosylated IgGs (Peter M. Bowers, et al., Methods 2014,65:44-56).
  • Transient expression systems are suitable for a single round of antigen selection before recovery of the antibody genes and therefore most useful for the selection of antibodies from smaller libraries.
  • Stable episomal vectors offer an attractive alternative. Episomal vectors can be transfected at high efficiency and stably maintained at low copy number, permitting multiple rounds of panning and the resolution of more complex antibody libraries.
  • the IgG library is based on germline sequence V-gene segments joined to rearranged (D)J regions isolated from a panel of human donors. RNA collected from 2000 human blood samples was reverse-transcribed into cDNA, and the V H and V K fragments were amplified using V H - and V K -specific primers and purified by gel extraction.
  • IgG libraries were generated by sub-cloning the V H and V K fragments into the display vectors containing IgG1 or K constant regions respectively and then electroporating into or transducing 293T cells.
  • scFvs were generated by linking V H and V K , and then sub-cloned into the display vector, which were then electroporated into or transduce 293T cells.
  • the IgG library is based on germline sequence V-gene segments joined to rearranged (D)J regions isolated from a panel of donors, the donor can be a mouse, rat, rabbit, or monkey.
  • Monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Patent No.4,816,567.
  • DNA encoding the monoclonal antibodies of the application can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies).
  • Hybridoma cells as described above or C5aR1- specific phage clones of the application can serve as a source of such DNA.
  • the DNA can be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells.
  • the DNA also can be modified, for example, by substituting the coding sequence for human heavy- and light-chain constant domains and/or framework regions in place of the homologous non-human sequences (U.S. Patent No.4,816,567; Morrison et al., supra) or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide.
  • the antibodies can be monovalent antibodies.
  • Methods for preparing monovalent antibodies are known in the art. For example, one method involves recombinant expression of immunoglobulin light chain and modified heavy chain. The heavy chain is truncated generally at any point in the Fc region so as to prevent heavy-chain crosslinking. Alternatively, the relevant cysteine residues are substituted with another amino acid residue or are deleted so as to prevent crosslinking.
  • In vitro methods are also suitable for preparing monovalent antibodies.
  • Antibody variable domains with the desired binding specificities can be fused to immunoglobulin constant-domain sequences.
  • the fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions.
  • the first heavy-chain constant region (CH1) containing the site necessary for light-chain binding is present in at least one of the fusions.
  • the anti-C5aR1 antibodies can be humanized antibodies or human antibodies.
  • Humanized forms of non-human (e.g., murine) antibody moieties are chimeric immunoglobulins, immunoglobulin chains, or fragments thereof (such as Fv, Fab, Fab', F(ab') 2 , scFv, or other antigen-binding subsequences of antibodies) that typically contain minimal sequence derived from non-human immunoglobulin.
  • Humanized antibody moieties include human immunoglobulins, immunoglobulin chains, or fragments thereof (recipient antibody) in which residues from a CDR of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat, or rabbit having the desired specificity, affinity, and capacity.
  • donor antibody such as mouse, rat, or rabbit having the desired specificity, affinity, and capacity.
  • Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues.
  • Humanized antibody moieties can also comprise residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences.
  • the humanized antibody can comprise substantially at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin, and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence.
  • a humanized antibody has one or more amino acid residues introduced into it from a source that is non-human. These non-human amino acid residues are often referred to as "import" residues, which are typically taken from an "import” variable domain.
  • humanization can be essentially performed following the method of Winter and co-workers (Jones et al., Nature, 321: 522-525 (1986); Riechmann et al., Nature, 332: 323-327 (1988); Verhoeyen et al., Science, 239: 1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody.
  • rodent CDRs or CDR sequences for the corresponding sequences of a human antibody.
  • such "humanized" antibody moieties are antibody moieties (U.S. Patent No.4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species.
  • humanized antibody moieties are typically human antibody moieties in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.
  • human antibody moieties can be generated. For example, it is now possible to produce transgenic animals (e.g., mice) that are capable, upon immunization, of producing a full repertoire of human antibodies in the absence of endogenous immunoglobulin production. For example, it has been described that the homozygous deletion of the antibody heavy-chain joining region (JH) gene in chimeric and germ-line mutant mice results in complete inhibition of endogenous antibody production.
  • JH antibody heavy-chain joining region
  • human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed that closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S.
  • amino acid sequences of the anti-C5aR1 antibody variants are contemplated.
  • Amino acid sequences of an antibody variant may be prepared by introducing appropriate modifications into the nucleotide sequence encoding the antibody, or by peptide synthesis. Such modifications include, for example, deletions from, and/or insertions into and/or substitutions of residues within the amino acid sequences of the antibody.
  • anti-C5aR1 antibody variants having one or more amino acid substitutions are provided.
  • Sites of interest for substitutional mutagenesis include the HVRs and FRs.
  • Amino acid substitutions may be introduced into an antibody of interest and the products screened for a desired activity, e.g., improved bioactivity, retained/improved antigen binding, decreased immunogenicity, or improved ADCC or CDC.
  • Conservative substitutions are shown in Table 4 below.
  • Amino acids may be grouped into different classes according to common side- chain properties: a. hydrophobic: Norleucine, Met, Ala, Val, Leu, Ile; b. neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; c. acidic: Asp, Glu; d. basic: His, Lys, Arg; e. residues that influence chain orientation: Gly, Pro; f. aromatic: Trp, Tyr, Phe. [00461] Non-conservative substitutions will entail exchanging a member of one of these classes for another class.
  • An exemplary substitutional variant is an affinity matured antibody, which may be conveniently generated, e.g., using phage display-based affinity maturation techniques. Briefly, one or more CDR residues are mutated and the variant antibody moieties displayed on phage and screened for a particular biological activity (e.g., bioactivity based on neutrophil C5a-induced CD11b upregulation inhibition assay or binding affinity). Alterations (e.g., substitutions) may be made in HVRs, e.g., to improve bioactivity based on neutrophil C5a-induced CD11b upregulation inhibition assay or binding affinity.
  • HVR hotspots
  • SDRs specificity determining residues
  • variable genes chosen for maturation are introduced into the variable genes chosen for maturation by any of a variety of methods (e.g., error-prone PCR, chain shuffling, or oligonucleotide-directed mutagenesis).
  • a secondary library is then created. The library is then screened to identify any antibody variants with the desired affinity.
  • Another method to introduce diversity involves HVR-directed approaches, in which several HVR residues (e.g., 4-6 residues at a time) are randomized. HVR residues involved in antigen binding may be specifically identified, e.g., using alanine scanning mutagenesis or modeling. CDR-H3 and CDR-L3 in particular are often targeted.
  • substitutions, insertions, or deletions may occur within one or more HVRs so long as such alterations do not substantially reduce the ability of the antibody to bind antigen.
  • conservative alterations e.g., conservative substitutions as provided herein
  • Such alterations may be outside of HVR "hotspots" or SDRs.
  • each HVR either is unaltered, or contains no more than one, two or three amino acid substitutions.
  • a useful method for identification of residues or regions of an antibody that may be targeted for mutagenesis is called "alanine scanning mutagenesis" as described by Cunningham and Wells (1989) Science, 244:1081-1085.
  • a residue or group of target residues e.g., charged residues such as Arg, Asp, His, Lys, and Glu
  • a neutral or negatively charged amino acid e.g., Ala or Glu
  • a crystal structure of an antigen-antibody complex can be determined to identify contact points between the antibody and antigen. Such contact residues and neighboring residues may be targeted or eliminated as candidates for substitution. Variants may be screened to determine whether they contain the desired properties.
  • Amino acid sequence insertions include amino- and/or carboxyl-terminal fusions ranging in length from one residue to polypeptides containing a hundred or more residues, as well as intrasequence insertions of single or multiple amino acid residues. Examples of terminal insertions include an antibody with an N-terminal methionyl residue.
  • Fc Region Variants include the fusion to the N- or C-terminus of the antibody to an enzyme (e.g., for ADEPT) or a polypeptide which increases the serum half-life of the antibody.
  • Fc Region Variants [00467]
  • one or more amino acid modifications may be introduced into the Fc region of an antibody (e.g., a full-length anti-C5aR1 antibody or anti- C5aR1 Fc fusion protein) provided herein, thereby generating an Fc region variant.
  • the Fc region variant has enhanced ADCC effector function, often related to binding to Fc receptors (FcRs).
  • the Fc region variant has decreased ADCC effector function.
  • ADCC Antibody-Dependent Cell-Mediated Cytotoxicity
  • ADCC is a cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell (e.g., a cancer cell), whose membrane-surface antigens have been bound by specific antibodies (e.g., an anti-C5aR1 antibody).
  • a target cell e.g., a cancer cell
  • specific antibodies e.g., an anti-C5aR1 antibody.
  • the typical ADCC involves activation of NK cells by antibodies.
  • An NK cell expresses CD16 which is an Fc receptor. This receptor recognizes, and binds to, the Fc portion of an antibody bound to the surface of a target cell.
  • the most common Fc receptor on the surface of an NK cell is called CD16 or Fc ⁇ RIII.
  • Binding of the Fc receptor to the Fc region of an antibody results in NK cell activation, release of cytolytic granules and consequent target cell apoptosis.
  • the contribution of ADCC to tumor cell killing can be measured with a specific test that uses NK-92 cells that have been transfected with a high- affinity FcR. Results are compared to wild-type NK-92 cells that do not express the FcR.
  • the application contemplates an anti-C5aR1 antibody variant (such as a full-length anti-C5aR1 antibody variant) comprising an Fc region that possesses some but not all effector functions, which makes it a desirable candidate for applications in which the half-life of the anti-C5aR1 antibody in vivo is important yet certain effector functions (such as CDC and ADCC) are unnecessary or deleterious.
  • an anti-C5aR1 antibody variant such as a full-length anti-C5aR1 antibody variant
  • an Fc region that possesses some but not all effector functions
  • Fc receptor (FcR) binding assays can be conducted to ensure that the antibody lacks Fc ⁇ R binding (hence likely lacking ADCC activity), but retains FcRn binding ability.
  • FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol. 9:457-492 (1991).
  • Non-limiting examples of in vitro assays to assess ADCC activity of a molecule of interest is described in U.S. Pat.
  • PBMC peripheral blood mononuclear cells
  • NK Natural Killer
  • ADCC activity of the molecule of interest may be assessed in vivo, e.g., in an animal model such as that disclosed in Clynes et al., Proc. Nat'l Acad. Sci. USA 95:652-656 (1998).
  • C1q binding assays may also be carried out to confirm that the antibody is unable to bind C1q and hence lacks CDC activity.
  • a CDC assay may be performed (see, for example, Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996); Cragg, M. S. et al., Blood 101:1045-1052 (2003); and Cragg, M. S. and M. J. Glennie, Blood 103:2738-2743 (2004)).
  • FcRn binding and in vivo clearance/half-life determinations can also be performed using methods known in the art (see, e.g., Petkova, S. B.
  • Antibodies with reduced effector function include those with substitution of one or more of Fc region residues 238, 265, 269, 270, 297, 327 and 329 (U.S. Pat. No. 6,737,056). Such Fc mutants include Fc mutants with substitutions at two or more of amino acid positions 265, 269, 270, 297 and 327, including the so-called "DANA" Fc mutant with substitution of residues 265 and 297 to alanine (U.S. Pat. No.7,332,581). [00471] Certain antibody variants with improved or diminished binding to FcRs are described.
  • an anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) variant comprising a variant Fc region comprising one or more amino acid substitutions which improve ADCC.
  • the variant Fc region comprises one or more amino acid substitutions which improve ADCC, wherein the substitutions are at positions 298, 333, and/or 334 of the variant Fc region (EU numbering of residues).
  • the anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) variant comprises the following amino acid substitution in its variant Fc region: S298A, E333A, and K334A.
  • alterations are made in the Fc region that result in altered (i.e., either improved or diminished) C1q binding and/or Complement Dependent Cytotoxicity (CDC), e.g., as described in U.S. Pat. No.6,194,551, WO 99/51642, and Idusogie et al., J. Immunol.164: 4178-4184 (2000).
  • CDC Complement Dependent Cytotoxicity
  • an anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) variant comprising a variant Fc region comprising one or more amino acid substitutions which increase half-life and/or improve binding to the neonatal Fc receptor (FcRn).
  • FcRn neonatal Fc receptor
  • Antibodies with increased half-lives and improved binding to FcRn are described in US2005/0014934A1 (Hinton et al.). Those antibodies comprise an Fc region with one or more substitutions therein which improve binding of the Fc region to FcRn.
  • Such Fc variants include those with substitutions at one or more of Fc region residues: 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or 434, e.g., substitution of Fc region residue 434 (U.S. Pat. No.7,371,826).
  • Fc region residue 434 U.S. Pat. No.7,371,826.
  • Anti-C5aR1 antibodies (such as full-length anti-C5aR1 antibodies) comprising any of the Fc variants described herein, or combinations thereof, are contemplated.
  • Glycosylation Variants [00477]
  • an anti-C5aR1 antibody (such as a full-length anti- C5aR1 antibody) provided herein is altered to increase or decrease the extent to which the anti-C5aR1 antibody is glycosylated. Addition or deletion of glycosylation sites to an anti- C5aR1 antibody may be conveniently accomplished by altering the amino acid sequence of the anti-C5aR1 antibody or polypeptide portion thereof such that one or more glycosylation sites are created or removed.
  • the anti-C5aR1 antibody comprises an Fc region
  • the carbohydrate attached thereto may be altered.
  • Native antibodies produced by mammalian cells typically comprise a branched, biantennary oligosaccharide that is generally attached by an N-linkage to Asn297 of the CH2 domain of the Fc region. See, e.g., Wright et al., TIBTECH 15:26-32 (1997).
  • the oligosaccharide may include various carbohydrates, e.g., mannose, N-acetyl glucosamine (GlcNAc), galactose, and sialic acid, as well as a fucose attached to a GlcNAc in the "stem" of the biantennary oligosaccharide structure.
  • modifications of the oligosaccharide in an anti-C5aR1 antibody of the application may be made in order to create anti-C5aR1 antibody variants with certain improved properties.
  • the N-glycans attached to the CH2 domain of Fc is heterogeneous.
  • Antibodies or Fc fusion proteins generated in CHO cells are fucosylated by fucosyltransferase activity. See Shoji-Hosaka et al., J. Biochem.2006, 140:777- 83. Normally, a small percentage of naturally occurring afucosylated IgGs may be detected in human serum. N-glycosylation of the Fc is important for binding to Fc ⁇ R; and afucosylation of the N-glycan increases Fc's binding capacity to Fc ⁇ RIIIa. Increased Fc ⁇ RIIIa binding can enhance ADCC, which can be advantageous in certain antibody therapeutic applications in which cytotoxicity is desirable.
  • an enhanced effector function can be detrimental when Fc-mediated cytotoxicity is undesirable.
  • the Fc fragment or CH2 domain is not glycosylated.
  • the N-glycosylation site in the CH2 domain is mutated to prevent from glycosylation.
  • anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) variants are provided comprising an Fc region wherein a carbohydrate structure attached to the Fc region has reduced fucose or lacks fucose, which may improve ADCC function.
  • anti-C5aR1 antibodies are contemplated herein that have reduced fucose relative to the amount of fucose on the same anti-C5aR1 antibody produced in a wild- type CHO cell. That is, they are characterized by having a lower amount of fucose than they would otherwise have if produced by native CHO cells (e.g., a CHO cell that produce a native glycosylation pattern, such as, a CHO cell containing a native FUT8 gene).
  • the anti-C5aR1 antibody is one wherein less than about 50%, 40%, 30%, 20%, 10%, or 5% of the N-linked glycans thereon comprise fucose.
  • the amount of fucose in such an anti-C5aR1 antibody may be from 1% to 80%, from 1% to 65%, from 5% to 65% or from 20% to 40%.
  • the anti-C5aR1 antibody is one wherein none of the N-linked glycans thereon comprise fucose, i.e., wherein the anti-C5aR1 antibody is completely without fucose, or has no fucose or is afucosylated.
  • the amount of fucose is determined by calculating the average amount of fucose within the sugar chain at Asn297, relative to the sum of all glycostructures attached to Asn 297 (e.g., complex, hybrid and high mannose structures) as measured by MALDI-TOF mass spectrometry, as described in WO 2008/077546, for example.
  • Asn297 refers to the asparagine residue located at about position 297 in the Fc region (EU numbering of Fc region residues); however, Asn297 may also be located about ⁇ 3 amino acids upstream or downstream of position 297, i.e., between positions 294 and 300, due to minor sequence variations in antibodies. Such fucosylation variants may have improved ADCC function.
  • Anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) variants are further provided with bisected oligosaccharides, e.g., in which a biantennary oligosaccharide attached to the Fc region of the anti-C5aR1 antibody is bisected by GlcNAc.
  • Such anti- C5aR1 antibody (such as a full-length anti-C5aR1 antibody) variants may have reduced fucosylation and/or improved ADCC function. Examples of such antibody variants are described, e.g., in WO 2003/011878 (Jean-Mairet et al.); U.S. Pat.
  • Anti-C5aR1 antibody (such as full-length anti-C5aR1 antibody) variants with at least one galactose residue in the oligosaccharide attached to the Fc region are also provided.
  • Such anti-C5aR1 antibody variants may have improved CDC function.
  • Such antibody variants are described, e.g., in WO 1997/30087 (Patel et al.); WO 1998/58964 (Raju, S.); and WO 1999/22764 (Raju, S.).
  • the anti-C5aR1 antibody (such as a full-length anti- C5aR1 antibody) variants comprising an Fc region are capable of binding to an Fc ⁇ RIII.
  • the anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) variants comprising an Fc region have ADCC activity in the presence of human effector cells (e.g., T cell) or have increased ADCC activity in the presence of human effector cells compared to the otherwise same anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) comprising a human wild-type IgG1Fc region.
  • cysteine engineered anti- C5aR1 antibodies such as a full-length anti-C5aR1 antibody
  • one or more amino acid residues are substituted with cysteine residues.
  • the substituted residues occur at accessible sites of the anti-C5aR1 antibody.
  • reactive thiol groups are thereby positioned at accessible sites of the anti- C5aR1 antibody and may be used to conjugate the anti-C5aR1 antibody to other moieties, such as drug moieties or linker-drug moieties, to create an anti-C5aR1 immunoconjugate, as described further herein.
  • Cysteine engineered anti-C5aR1 antibodies may be generated as described, e.g., in U.S. Pat. No.7,521,541.
  • an anti-C5aR1 antibody (such as a full-length anti- C5aR1 antibody) provided herein may be further modified to contain additional non- proteinaceous moieties that are known in the art and readily available.
  • the moieties suitable for derivatization of the anti-C5aR1 antibody include but are not limited to water soluble polymers.
  • Non-limiting examples of water soluble polymers include, but are not limited to, polyethylene glycol (PEG), copolymers of ethylene glycol/propylene glycol, carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone, poly-1,3- dioxolane, poly-1,3,6-trioxane, ethylene/maleic anhydride copolymer, polyaminoacids (either homopolymers or random copolymers), and dextran or poly(n-vinyl pyrrolidone)polyethylene glycol, propropylene glycol homopolymers, prolypropylene oxide/ethylene oxide co- polymers, polyoxyethylated polyols (e.g., glycerol), polyvinyl alcohol, and mixtures thereof.
  • PEG polyethylene glycol
  • copolymers of ethylene glycol/propylene glycol carboxymethylcellulose
  • dextran polyvinyl alcohol
  • Polyethylene glycol propionaldehyde may have advantages in manufacturing due to its stability in water.
  • the polymer may be of any molecular weight, and may be branched or unbranched.
  • the number of polymers attached to the anti-C5aR1 antibody may vary, and if more than one polymer are attached, they can be the same or different molecules. In general, the number and/or type of polymers used for derivatization can be determined based on considerations including, but not limited to, the particular properties or functions of anti- C5aR1 antibody to be improved, whether the anti-C5aR1 antibody derivative will be used in a therapy under defined conditions, etc.
  • compositions comprising any of the anti-C5aR1 antibodies (such as a full-length anti-C5aR1 antibody), nucleic acids encoding the antibodies, vectors comprising the nucleic acids encoding the antibodies, or host cells comprising the nucleic acids or vectors described herein.
  • a pharmaceutical composition comprising any one of the anti-C5aR1 antibodies described herein and a pharmaceutically acceptable carrier.
  • Suitable formulations of the anti-C5aR1 antibodies are obtained by mixing an anti-C5aR1 antibody having the desired degree of purity with optional pharmaceutically acceptable carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions.
  • Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propylparaben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as olyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine
  • lyophilized formulations adapted for subcutaneous administration are described in WO97/04801. Such lyophilized formulations may be reconstituted with a suitable diluent to a high protein concentration and the reconstituted formulation may be administered subcutaneously to the individual to be treated herein. Lipofectins or liposomes can be used to deliver the anti-C5aR1 antibodies of this application into cells.
  • the formulation herein may also contain one or more active compounds in addition to the anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other.
  • an anti-neoplastic agent for example, it may be desirable to further provide an anti-neoplastic agent, a growth inhibitory agent, a cytotoxic agent, or a chemotherapeutic agent in addition to the anti-C5aR1 antibody.
  • Such molecules are suitably present in combination in amounts that are effective for the purpose intended.
  • the effective amount of such other agents depends on the amount of anti-C5aR1 antibody present in the formulation, the type of disease or disorder or treatment, and other factors discussed above. These are generally used in the same dosages and with administration routes as described herein or about from 1 to 99% of the heretofore employed dosages.
  • the anti-C5aR1 antibodies may also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules) or in macroemulsions. Sustained-release preparations may be prepared.
  • colloidal drug delivery systems for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules
  • Sustained-release preparations may be prepared.
  • Sustained-release preparations of the anti-C5aR1 antibodies can be prepared.
  • suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody (or fragment thereof), which matrices are in the form of shaped articles, e.g., films, or microcapsules.
  • sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate ), or poly(vinylalcohol)), polylactides (U.S. Pat.
  • copolymers of L-glutamic acid and ethyl-L-glutamate non-degradable ethylene-vinyl acetate
  • degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOTTM (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate)
  • poly-D (-)-3-hydroxybutyric acid While polymers such as ethylene- vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydro gels release proteins for shorter time periods.
  • encapsulated antibody When encapsulated antibody remain in the body for a long time, they can denature or aggregate as a result of exposure to moisture at 37°C, resulting in a loss of biological activity and possible changes in immunogenicity.
  • Rational strategies can be devised for stabilization of anti-C5aR1 antibodies depending on the mechanism involved. For example, if the aggregation mechanism is discovered to be intermolecular S-S bond formation through thio-disulfide interchange, stabilization can be achieved by modifying sulfhydryl residues, lyophilizing from acidic solutions, controlling moisture content, using appropriate additives, and developing specific polymer matrix compositions.
  • the anti-C5aR1 antibody (such as a full-length anti- C5aR1 antibody) is formulated in a buffer comprising a citrate, NaCl, acetate, succinate, glycine, polysorbate 80 (Tween 80), or any combination of the foregoing.
  • a buffer comprising a citrate, NaCl, acetate, succinate, glycine, polysorbate 80 (Tween 80), or any combination of the foregoing.
  • the formulations to be used for in vivo administration must be sterile. This is readily accomplished by, e.g., filtration through sterile filtration membranes.
  • anti-C5aR1 antibodies e.g., full-length anti-C5aR1 antibodies
  • compositions of the application can be administered to individuals (e.g., mammals such as humans) to treat a disease and/or disorder associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers).
  • a disease and/or disorder associated with C5aR1 signaling e.g., inflammatory diseases, autoimmune disease, or cancers.
  • These diseases include, but are not limited to allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies.
  • the present application thus in some embodiments provides a method of treating a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) in an individual comprising administering to the individual an effective amount of a composition (such as a pharmaceutical composition) comprising an anti-C5aR1 antibody (e.g., a full-length anti-C5aR1 antibody), such as any one of the anti- C5aR1 antibodies (e.g., full-length anti-C5aR1 antibodies) described herein.
  • the individual is human.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) specifically binding to an epitope on human C5aR1 , wherein the epitope comprises amino acid residues of human C5aR1.
  • an anti-C5aR1 antibody e.g., full-length anti-C5aR1 antibody
  • the anti-C5aR1 antibody is a full-length antibody.
  • the full-length anti- C5aR1 antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies.
  • the individual is human.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising SYWMN (SEQ ID NO: 1); an HC-CDR2 comprising RIDPX 1 X 2 X 3 X 4 TRYNQKFED (SEQ ID NO: 72), wherein X 1 is G, R, S, or Y, X 2 is D, R, or S, X 3 is G or S, and X 4 is E or G; and an HC- CDR3 comprising FVX1PX 2 GX3FX4Y (S
  • the anti-C5aR1 antibody is a full-length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-15, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-31, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-44, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a V H comprising the amino acid sequence of any one of SEQ ID NOs: 76-91 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 76-91, and a V L comprising the amino acid sequence of any one of SEQ ID NOs: 104-120, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 104- 120.
  • an anti-C5aR1 antibody e.g., full- length anti-C5aR1 antibody
  • V H comprising the amino acid sequence of any one of SEQ ID NOs: 76-91 or a variant thereof having at least about 80% sequence identity to the amino acid sequence
  • the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC- CDR2 compris
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 76 and a V L comprising the amino acid sequence of SEQ ID NO: 104.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 77 and a V L comprising the amino acid sequence of SEQ ID NO: 105.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 78 and a V L comprising the amino acid sequence of SEQ ID NO: 106.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 79 and a V L comprising the amino acid sequence of SEQ ID NO: 107.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 80 and a V L comprising the amino acid sequence of SEQ ID NO: 106.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 81 and a V L comprising the amino acid sequence of SEQ ID NO: 108.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of S
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 82 and a V L comprising the amino acid sequence of SEQ ID NO: 109.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of S
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 83 and a V L comprising the amino acid sequence of SEQ ID NO: 110.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 83 and a V L comprising the amino acid sequence of SEQ ID NO: 111.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 84 and a V L comprising the amino acid sequence of SEQ ID NO: 112.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 85 and a V L comprising the amino acid sequence of SEQ ID NO: 113.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of S
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 86 and a V L comprising the amino acid sequence of SEQ ID NO: 107.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 87 and a V L comprising the amino acid sequence of SEQ ID NO: 114.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 88 and a V L comprising the amino acid sequence of SEQ ID NO: 115.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 89 and a V L comprising the amino acid sequence of SEQ ID NO: 116.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 90 and a V L comprising the amino acid sequence of SEQ ID NO: 117.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 91 and a V L comprising the amino acid sequence of SEQ ID NO: 118.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 89 and a V L comprising the amino acid sequence of SEQ ID NO: 119.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 89 and a V L comprising the amino acid sequence of SEQ ID NO: 120.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a heavy chain variable domain (V H ) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising SGYSWH (SEQ ID NO: 2); an HC-CDR2 comprising YIHSSGDTDYNPSLKR (SEQ ID NO: 16); and an HC-CDR3 comprising SIGDY (SEQ ID NO: 32); and a light chain variable domain (V L ) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 45); an LC-CDR2
  • the anti-C5aR1 antibody is a full-length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a V H comprising the amino acid sequence of any one of SEQ ID NOs: 92-96 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 92-96, and a V L comprising the amino acid sequence of any one of SEQ ID NOs: 121-127, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 121- 127.
  • an anti-C5aR1 antibody e.g., full- length anti-C5aR1 antibody
  • V H comprising the amino acid sequence of any one of SEQ ID NOs: 92-96 or a variant thereof having at least about 80% sequence identity to the amino acid
  • the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC- CDR2
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 92 and a V L comprising the amino acid sequence of SEQ ID NO: 121.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 93 and a V L comprising the amino acid sequence of SEQ ID NO: 122.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 93 and a V L comprising the amino acid sequence of SEQ ID NO: 123.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 93 and a V L comprising the amino acid sequence of SEQ ID NO: 124.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 94 and a V L comprising the amino acid sequence of SEQ ID NO: 125.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 95 and a V L comprising the amino acid sequence of SEQ ID NO: 126.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 96 and a V L comprising the amino acid sequence of SEQ ID NO: 127.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 96 and a V L comprising the amino acid sequence of SEQ ID NO: 124.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 96 and a V L comprising the amino acid sequence of SEQ ID NO: 125.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the anti-C5aR1 antibody provided herein comprises a V H comprising the amino acid sequence of SEQ ID NO: 96 and a V L comprising the amino acid sequence of SEQ ID NO: 126.
  • the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino
  • the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a V H comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 97, and a V L comprising the amino acid sequence of SEQ ID NO: 128, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 128.
  • an anti-C5aR1 antibody e.g., full- length anti-C5aR1 antibody
  • V H comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 97
  • V L comprising the amino acid sequence of SEQ ID NO: 128, or a variant thereof
  • the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC- C
  • the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a V H comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 98, and a V L comprising the amino acid sequence of SEQ ID NO: 129, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 129.
  • an anti-C5aR1 antibody e.g., full- length anti-C5aR1 antibody
  • V H comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 98
  • V L comprising the amino acid sequence of SEQ ID NO: 129, or a
  • the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC- C
  • the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a V H comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 99, and a V L comprising the amino acid sequence of SEQ ID NO: 130, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 130.
  • an anti-C5aR1 antibody e.g., full- length anti-C5aR1 antibody
  • V H comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 99
  • a V L comprising the amino acid sequence of SEQ ID NO: 130, or a variant thereof having at least
  • the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an LC- CDR
  • the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a V H comprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 100, and a V L comprising the amino acid sequence of SEQ ID NO: 131, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 131.
  • an anti-C5aR1 antibody e.g., full- length anti-C5aR1 antibody
  • the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 48, an LC- C
  • the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a V H comprising the amino acid sequence of SEQ ID NO: 101 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 101, and a V L comprising the amino acid sequence of SEQ ID NO: 132, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 132.
  • an anti-C5aR1 antibody e.g., full- length anti-C5aR1 antibody
  • the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an LC- C
  • the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a V H comprising the amino acid sequence of SEQ ID NO: 102 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 102, and a V L comprising the amino acid sequence of SEQ ID NO: 133, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 133.
  • an anti-C5aR1 antibody e.g., full- length anti-C5aR1 antibody
  • V H comprising the amino acid sequence of SEQ ID NO: 102 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 102
  • V L comprising the amino acid sequence of SEQ ID NO: 133, or a
  • the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 50, an LC- C
  • the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies.
  • the individual is human.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a V H comprising the amino acid sequence of SEQ ID NO: 103 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 103, and a V L comprising the amino acid sequence of SEQ ID NO: 134, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 134.
  • an anti-C5aR1 antibody e.g., full- length anti-C5aR1 antibody
  • V H comprising the amino acid sequence of SEQ ID NO: 103 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 103
  • V L comprising the amino acid sequence of SEQ ID NO: 134, or a
  • the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a V H comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a V L comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC- C
  • the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human.
  • a method of treating an individual having a disease or condition associated with C5aR1 signaling comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a V H comprising the amino acid sequence of SEQ ID NO: 102 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 102, and a V L comprising the amino acid sequence of SEQ ID NO: 135, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 135.
  • an anti-C5aR1 antibody e.g., full- length anti-C5aR1 antibody
  • V H comprising the amino acid sequence of SEQ ID NO: 102 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 102
  • V L comprising the amino acid sequence of SEQ ID NO: 135, or a variant thereof having
  • the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139.
  • the individual is a mammal (e.g., human, non-human primate, rat, mouse, cow, horse, pig, sheep, goat, dog, cat, etc.). In some embodiments, the individual is a human. In some embodiments, the individual is a clinical patient, a clinical trial volunteer, an experimental animal, etc. In some embodiments, the individual is younger than about 60 years old (including for example younger than about any of 50, 40, 30, 25, 20, 15, or 10 years old). In some embodiments, the individual is older than about 60 years old (including for example older than about any of 70, 80, 90, or 100 years old).
  • the individual is diagnosed with or genetically prone to one or more of the diseases or disorders described herein (such as inflammatory diseases, autoimmune disease, or cancers ). In some embodiments, the individual has one or more risk factors associated with one or more diseases or disorders described herein.
  • the present application in some embodiments provides a method of delivering an anti-C5aR1 antibody (such as any one of the anti-C5aR1 antibodies described herein, e.g., an isolated anti-C5aR1 antibody) to a cell producing C5aR1 in an individual, the method comprising administering to the individual a composition comprising the anti-C5aR1 antibody.
  • the anti-C5aR1 antibodies e.g., full-length anti-C5aR1 antibodies
  • compositions of the application are administered in combination with a second, third, or fourth agent (including, e.g., radiation therapy, chemotherapy, therapy for autoimmune disease or other drug therapy (e.g., corticosteroid therapy)) to treat diseases or disorders associated with C5aR1 signaling.
  • a second, third, or fourth agent including, e.g., radiation therapy, chemotherapy, therapy for autoimmune disease or other drug therapy (e.g., corticosteroid therapy)
  • Cancer treatments can be evaluated by, e.g., tumor regression, tumor weight or size shrinkage, time to progression, duration of survival, progression free survival, overall response rate, duration of response, quality of life, protein expression and/or activity.
  • the efficacy of treatment is measured as the percentage tumor growth inhibition (% TGI), calculated using the equation 100-(T/C ⁇ 100), where T is the mean relative tumor volume of the treated tumor, and C is the mean relative tumor volume of a non-treated tumor.
  • % TGI percentage tumor growth inhibition
  • the %TGI is about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, or more than 95%.
  • the efficacy of treatment is measured using shape change of granulocytes and/or increase in the survival of granulocytes. In some embodiments, the efficacy of treatment is measured by the increase of cytokine secretion by monocytes. [00576] In some embodiments, the efficiency of treatment is measured as the percentage human neutrophils migration inhibition. In some embodiments, the antibody inhibits migration to less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% compared to the level of migration observed in the presence of 10nM C5a and no anti- C5aR antibody.
  • the efficiency of treatment can be evaluated by, e.g., the inhibition of C5a induced neutrophil maturation based on secondary effects such as CD11b and CD62L expression.
  • CD11b and CD62L are maturation markers of neutrophils as they are up and down-regulated, respectively, upon activation by C5a/C5aR interaction.
  • the IC50 as determined in an CD11b upregulation assay is below 3.5 ⁇ g/ml, such as 3.0 ⁇ g/ml, such as 2.5 ⁇ g/ml, such as 2.0 ⁇ g/ml, or such as 1.5 ⁇ g/ml or even below such as 1.0 ⁇ g/ml.
  • the dose of the anti-C5aR1 antibody (such as isolated anti-C5aR1 antibody) compositions administered to an individual may vary with the particular composition, the mode of administration, and the type of disease being treated.
  • the amount of the composition (such as composition comprising isolated anti- C5aR1 antibody) is effective to result in an objective response (such as a partial response or a complete response) in the treatment of inflammatory diseases, autoimmune disease, or cancers.
  • the amount of the anti-C5aR1 antibody composition is sufficient to result in a complete response in the individual.
  • the amount of the anti-C5aR1 antibody composition is sufficient to result in a partial response in the individual. In some embodiments, the amount of the anti-C5aR1 antibody composition administered (for example when administered alone) is sufficient to produce an overall response rate of more than about any of 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 64%, 65%, 70%, 75%, 80%, 85%, or 90% among a population of individuals treated with the anti-C5aR1 antibody composition. Responses of an individual to the treatment of the methods described herein can be determined, for example, based on RECIST level or human neutrophils migration inhibition level.
  • the amount of the composition is sufficient to control symptoms and reduce the risk of exacerbations of the individual. In some embodiments, the amount of the composition is sufficient to control symptoms and reduce the risk of exacerbations of the individual. In some embodiments, the amount of the composition (for example when administered along) is sufficient to produce clinical benefit of more than about any of 50%, 60%, 70%, or 77% among a population of individuals treated with the anti-C5aR1 antibody composition.
  • the amount of the composition is an amount sufficient to control symptoms and reduce the risk of exacerbations in the same subject prior to treatment or compared to the corresponding activity in other subjects not receiving the treatment.
  • Standard methods can be used to measure the magnitude of this effect, such as in vitro assays with purified enzyme, cell-based assays, animal models, or human testing.
  • the amount of the anti-C5aR1 antibody (such as a full- length anti-C5aR1 antibody) in the composition is below the level that induces a toxicological effect (i.e., an effect above a clinically acceptable level of toxicity) or is at a level where a potential side effect can be controlled or tolerated when the composition is administered to the individual.
  • the amount of the composition is close to a maximum tolerated dose (MTD) of the composition following the same dosing regimen.
  • the amount of the composition is more than about any of 80%, 90%, 95%, or 98% of the MTD.
  • the amount of an anti-C5aR1 antibody (such as a full- length anti-C5aR1 antibody) in the composition is included in a range of about 0.001 ⁇ g to about 1000 ⁇ g.
  • the effective amount of anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) in the composition is in the range of about 0.1 ⁇ g/kg to about 100 mg/kg of total body weight.
  • the anti-C5aR1 antibody compositions can be administered to an individual (such as human) via various routes, including, for example, intravenous, intra-arterial, intraperitoneal, intrapulmonary, oral, inhalation, intravesicular, intramuscular, intra-tracheal, subcutaneous, intraocular, intrathecal, transmucosal or transdermal.
  • sustained continuous release formulation of the composition may be used.
  • the composition is administered inhaled.
  • the composition is administered intravenously.
  • the composition is administered intraportally.
  • the composition is administered intraarterially.
  • the composition is administered intraperitoneally.
  • the composition is administered intrahepatically. In some embodiments, the composition is administered by hepatic arterial infusion. In some embodiments, the administration is to an injection site distal to a first disease site.
  • Articles of Manufacture and Kits [00586]
  • an article of manufacture containing materials useful for the treatment of disease or condition associated with C5aR1 signaling, (e.g., inflammatory diseases, autoimmune disease, or cancers) or for delivering an anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) to a cell producing C5aR1 of the individual.
  • the article of manufacture can comprise a container and a label or package insert on or associated with the container.
  • Suitable containers include, for example, bottles, vials, syringes, etc.
  • the containers may be formed from a variety of materials such as glass or plastic.
  • the container holds a composition which is effective for treating a disease or disorder described herein, and may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle).
  • At least one active agent in the composition is an anti-C5aR1 antibody of the application.
  • the label or package insert indicates that the composition is used for treating the particular condition.
  • the label or package insert will further comprise instructions for administering the anti-C5aR1 antibody composition to the patient.
  • Package insert refers to instructions customarily included in commercial packages of therapeutic products that contain information about the indications, usage, dosage, administration, contraindications and/or warnings concerning the use of such therapeutic products.
  • the package insert indicates that the composition is used for treating disease or condition associated with C5aR1 signaling (such as inflammatory diseases, autoimmune disease, or cancers).
  • the package insert indicates that the composition is used for treating disease or condition selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies.
  • the article of manufacture may further comprise a second container comprising a pharmaceutically-acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution or dextrose solution.
  • BWFI bacteriostatic water for injection
  • phosphate-buffered saline such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution or dextrose solution.
  • Kits are also provided that are useful for various purposes, e.g., for treatment of disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers), or for delivering an anti-C5aR1 antibody (such as a full- length anti-C5aR1 antibody) to a cell producing C5aR1 of the individual, optionally in combination with the articles of manufacture.
  • C5aR1 signaling e.g., inflammatory diseases, autoimmune disease, or cancers
  • an anti-C5aR1 antibody such as a full- length anti-C5aR1 antibody
  • Kits of the application include one or more containers comprising anti-C5aR1 antibody composition (or unit dosage form and/or article of manufacture), and in some embodiments, further comprise another agent (such as the agents described herein) and/or instructions for use in accordance with any of the methods described herein.
  • the kit may further comprise a description of selection of individuals suitable for treatment. Instructions supplied in the kits of the application are typically written instructions on a label or package insert (e.g., a paper sheet included in the kit), but machine- readable instructions (e.g., instructions carried on a magnetic or optical storage disk) are also acceptable.
  • the kit comprises a composition comprising an anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody).
  • the kit comprises a) a composition comprising any one of the anti-C5aR1 antibodies described herein, and b) an effective amount of at least one other agent, wherein the other agent enhances the effects (e.g., treatment effect, detecting effect) of the anti-C5aR1 antibody.
  • the kit comprises a) a composition comprising any one of the anti-C5aR1 antibodies described herein, and b) instructions for administering the anti- C5aR1 antibody composition to an individual for treatment of a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ).
  • a disease or condition associated with C5aR1 signaling e.g., inflammatory diseases, autoimmune disease, or cancers.
  • the kit comprises a) a composition comprising any one of the anti-C5aR1 antibodies described herein, b) an effective amount of at least one other agent, wherein the other agent enhances the effect (e.g., treatment effect, detecting effect) of the anti-C5aR1 antibody, and c) instructions for administering the anti-C5aR1 antibody composition and the other agent(s) to an individual for treatment of a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers .
  • the anti-C5aR1 antibody and the other agent(s) can be present in separate containers or in a single container.
  • the kit may comprise one distinct composition or two or more compositions wherein one composition comprises an anti-C5aR1 antibody and another composition comprises another agent.
  • the kit comprises a nucleic acid (or a set of nucleic acids) encoding an anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody).
  • the kit comprises a) a nucleic acid (or a set of nucleic acids) encoding an anti- C5aR1 antibody, and b) a host cell for expressing the nucleic acid (or a set of nucleic acids).
  • the kit comprises a) a nucleic acid (or a set of nucleic acids) encoding an anti-C5aR1 antibody, and b) instructions for i) expressing the anti-C5aR1 antibody in a host cell, ii) preparing a composition comprising the anti-C5aR1 antibody, and iii) administering the composition comprising the anti-C5aR1 antibody to an individual for the treatment of a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers.
  • a disease or condition associated with C5aR1 signaling e.g., inflammatory diseases, autoimmune disease, or cancers.
  • the kit comprises a) a nucleic acid (or a set of nucleic acids) encoding an anti-C5aR1 antibody, b) a host cell for expressing the nucleic acid (or a set of nucleic acids), and c) instructions for i) expressing the anti-C5aR1 antibody in the host cell, ii) preparing a composition comprising the anti-C5aR1 antibody, and iii) administering the composition comprising the anti-C5aR1 antibody to an individual for the treatment of a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ).
  • a disease or condition associated with C5aR1 signaling e.g., inflammatory diseases, autoimmune disease, or cancers.
  • Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (e.g., sealed Mylar or plastic bags), and the like. Kits may optionally provide additional components such as buffers and interpretative information.
  • the present application thus also provides articles of manufacture, which include vials (such as sealed vials), bottles, jars, flexible packaging, and the like.
  • the instructions relating to the use of the anti-C5aR1 antibody compositions generally include information as to dosage, dosing schedule, and route of administration for the intended treatment.
  • the containers may be unit doses, bulk packages (e.g., multi-dose packages) or sub-unit doses.
  • kits may be provided that contain sufficient dosages of an anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) as disclosed herein to provide effective treatment of an individual for an extended period, such as any of a week, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 7 months, 8 months, 9 months, or more. Kits may also include multiple unit doses of the anti-C5aR1 antibody and pharmaceutical compositions and instructions for use and packaged in quantities sufficient for storage and use in pharmacies, for example, hospital pharmacies and compounding pharmacies.
  • an anti-C5aR1 antibody such as a full-length anti-C5aR1 antibody
  • Example 1 Generation of C5aR1
  • This example illustrates the preparation of the various C5aR1 constructs used as antigens in eliciting and screening the anti-C5aR1 antibodies of the present disclosure.
  • the coding sequence of the human C5aR1 (huC5aR1), musculus C5aR1 (musC5aR1), or cynomolgus monkey C5aR1 (cynoC5aR1) was synthesized and sub-cloned into the expression vector pCDNA3.1 or LV101. The amino acid sequences were provided in Table 5.
  • C5aR1 polypeptide sequence Proteins were expressed in Expi293 cells and ExpiCHO (Thermo Fisher Scientific) according to the manufacturer’s protocol. Briefly, 293F or CHO cells were transfected with the expression vectors respectively, and the cells were cultured at 37°C, under 8% CO 2 and 120rpm for 5 days.
  • Example 2 Generation of Anti-C5aR1 Antibodies Using Hybridoma Methods, Screening and Characterization [0599] This example illustrates the methods of using mouse hybridoma technology to generate anti-C5aR1 antibodies, and methods to screen and select antibodies for further characterization.
  • huC5aR1 overexpressing cells [0601] To generate anti-C5aR1 antibodies and examine the binding of these antibodies to huC5aR1 overexpressing cells, Expi293 and ExpiCHO cells stably overexpressing huC5aR1 were used to perform FACS analysis. [0602] The coding sequence of huC5aR1 was cloned into a lentiviral vector (LV101) and the recombinant virus was packaged according to the instruction of the virus packaging kit (Lenti-XTM Packaging Single Shots, Cat# 631275, Takada).
  • mice were immunized with Expi293 cells. Two days later, mice were treated with cyclophosphamide to delete responding T and B cells. Deletion of responding cells was confirmed by flow cytometry with sera drawn from the mice. Lentiviral constructs coding for huC5aR1 were injected into the mice.
  • Expi293 cells overexpressing huC5aR1 were injected into the mice. Endpoint titers were determined by whole cell ELISA as described below. Three days after the last immunization, spleens and lymph nodes were harvested and processed according to standard protocols.
  • Mouse B cells were isolated by EasySep Mouse B cell isolation Kit (StemCell, cat# 19854A) and fused with myeloma cells SP2/0-Ag14 cells (ATCC, CRL 1581) using PEG. Following standard protocols, the fused cells were plated into six-well plates in semi-solid ClonalCell-HY Cloning-Medium D (StemCell, cat# 03804).
  • Monoclonal hybridoma clones were picked into 96 well/plate using Clone Pix 2 Machine (Molecular Devices) and cultured in HT medium.
  • Whole Cell ELISA assays After 10-14 days of culture, supernatants were collected and subjected to primary screening by ELISA performed on the surface of intact ExpiCHO cells overexpressing huC5aR1 in 96 well plates (Corning 3365). ExpiCHO cells overexpressing huC5aR1 (50,000/well) were plated in FACS buffer (1 ⁇ phosphate buffered saline, PBS; 5 mM EDTA; 1% BSA; pH7.4).
  • Hybridoma clones were confirmed by primary screen antigen binding whole cell ELISA. Positive clones were scaled up to 30 mL cultures in serum free medium and the antibodies were purified as follows. Supernatant media were clarified by centrifugation at 300g for 10 min to remove cells and by filtration with 0.22-micron filter. Clarified supernatant media was mixed with Protein A resin (Thermo Fisher Scientific, cat# A26458) equilibrated with PBS buffer and incubated with gentle rotation for 1.5 h at room temperature.
  • Protein A resin Thermo Fisher Scientific, cat# A26458
  • Expi293 cells overexpressing huC5aR1 (50,000/well) were plated in FACS buffer (1 ⁇ phosphate buffered saline, PBS; 5 mM EDTA; 1% BSA; pH7.4). 50 ⁇ L of the individual purified antibodies at the indicated concentration (typically titrations starting at 100nM decreasing in 5-fold increments) was added to individual well followed by incubation for 30 min at room temperature (RT; 25oC). Plates were washed 2 times with FACS buffer, then 50 ⁇ L/well of AF488-labeled anti-mouse IgG was added and incubated at RT for 30 min.
  • EC 50 values of the hybridoma anti-C5aR1 antibodies for top candidates are shown in Table 6.
  • Table 6 the exemplary hybridoma anti-C5aR1 antibodies could bind to huC5aR1.
  • the exemplary hybridoma antibodies 10G1, 6G5 and 1G2 could bind to cynoC5aR1 (data not shown).
  • the hybridoma C5aR1 antibodies listed in Table 6 did not bind to musC5aR1 (data not shown).
  • C5aR1-TEV/E-Arrestin-Luc reporter assay Dual transgenic U2OS cells bearing huC5aR1 coupled to tobacco etch virus (TEV) at the C terminus and E-Arrestin coupled to luciferase with a TEV cleavage site (hereinafter referred to as C5aR1-TEV/E-Arrestin-Luc cells) were used to determine functional inhibition of C5aR1 signal transduction. When C5a is added to these cells, E-Arrestin is recruited to the C5aR1.
  • TEV tobacco etch virus
  • C5aR1-coupled TEV enzyme then cleaves the TEV site in the luciferase protein allowing it to fold correctly and resulting in a luciferase signal when substrate is added to the cells.
  • C5aR1-TEV/E-Arrestin- Luc cells ⁇ BonOpus, Cat#BC050088 ⁇ were plated at 10,000 cells/well in 96-well or 3,000 cells/well in 384-well tissue culture-treated plates overnight at 37oC in McCoy’s media containing 10% FBS.
  • Luminescence values were recorded at each dilution and plotted as the log[Ab] and IC 50 values were determined in GraphPad Prism 6.0 and summarized in Table 7. [0609] As shown in Table 7, the exemplary hybridoma anti-C5aR1 antibodies exhibited good inhibition activity of C5aR1 function.
  • IC 50 values of the exemplary hybridoma anti-C5aR1 antibodies were summarized in Table 8. [0611] As shown in Table 8, the exemplary hybridoma anti-C5aR1 antibodies exhibited inhibition activity of C5a-induced CD11b upregulation in neutrophil.
  • RNA Extraction Monoclonal anti-huC5aR1 hybridoma hits were grown to a density of 1-3 ⁇ 10 5 in standard hybridoma medium (DMEM/F12, 10% FBS, 1% Glutamax, 1% pen/strep) for 7-10 days in a T75 flask with >80% cell viability. 1-3 million cells from cultures were pelleted in a 15 mL falcon tube after centrifugation at 300 g for 5 min. Pelleted cells were washed by 5 mL ice cold PBS.
  • standard hybridoma medium DMEM/F12, 10% FBS, 1% Glutamax, 1% pen/strep
  • PCR amplification to generate cDNA The synthesis of cDNA utilizes specific reverse PCR primers in conjunction with switch oligos for heavy and kappa chains. To generate cDNA, one microgram of RNA was used as a template followed by reverse transcription using SMART Scribe Reverse Transcriptase kit from Clontech (TAKARA, cat# 639537).
  • the reagents include 10 ⁇ M primers (Integrated DNA technologies), 10 mM deoxy nucleotide triphosphate mix (New England Biolab, cat# N0447S), H 2 O, and an 80 U/ ⁇ L RNAse inhibitor (Invitrogen, cat# 10000840).
  • the constant region-specific reverse primers were used in conjunction with universal forward primer in 5’-RACE PCR reactions. PCR products were gel purified and cloned into TOPO TA vectors (ThermoFisher, cat# 451641) which were then transformed into competent cells (ThermoFisher, cat# 451641). After transformation and blue/white screening, white colonies were picked and grew overnight in LB broth media containing carbenicillin.
  • the exemplary human heavy chain constant region and light chain constant region were shown in the Table 3.
  • the expression of recombinant anti-C5aR1 chimeric antibodies was performed using Expi293 expression system in accordance with the instruction provided.
  • the plasmids for the heavy chain and the light chain were co- transfected into the cells at the ratio of 1:1 and the transfected cells were cultured for 6 days before harvest.
  • Recombinant IgG molecules were purified as the following protocols. Supernatant media were clarified by centrifugation at 300 g for 10 min to remove cells and by filtration with 0.22 ⁇ m filter.
  • Clarified supernatant media were mixed with MabSelect Protein A resin equilibrated with PBS buffer and incubated with gentle rotation for 1.5 h at room temperature. After incubation, the slurry was loaded into a column and the resin was washed with 20 ⁇ column volumes of PBS buffer containing 0.15M NaCl, then eluted with 3 ⁇ column volumes of 50 mM sodium phosphate (pH 3.0). The pH of the eluent was quickly adjusted to pH 5.2 with 1 M Tris-HCl (pH 9.0) and the buffer was replaced by PBS buffer.
  • C5a Receptor binding assay The binding of chimeric anti-C5aR1 antibodies to huC5aR1 overexpressing cells was examined as described above in Example 2. Binding EC 50 values for exemplary chimeric antibodies were displayed in Figure 1A. [0619] As shown in Figure 1A, the exemplary chimeric anti-C5aR1 antibodies 10G1 and 1C2 exhibited comparable binding activity to huC5aR1 as compared to their hybridoma antibodies and the chimeric format did not alter their binding function.
  • C5aR1-TEV/E-Arrestin-Luc reporter assay Assays using the C5aR1-TEV/E-Arrestin- Luc reporter cells and inhibition of labeled-C5a binding were performed as described above in Example 2. IC 50 values for exemplary chimeric anti-C5aR1 antibodies were displayed in Figure 1B. [0621] As shown in Figure 1B, the exemplary chimeric anti-C5aR1 antibodies 10G1 and 1C2 showed comparable inhibition activity of C5aR1 function as compared to their hybridoma antibodies.
  • Example 4 Preparation of Humanized Versions of 10G1 and 1C2
  • This example illustrates the preparation of humanized versions of the murine anti- huC5aR1 antibody derived from the hybridoma clone 10G1 and 1C2.
  • Humanization of anti-huC5aR1 antibody [0624] The light chain variable region (V L ) and heavy chain variable region (V H ) sequences of murine antibody from hybridoma 10G1 and 1C2 were aligned to human germline antibody sequences respectively.
  • the human germline kappa light chain (Gene ID–V gene: IGKV2_24*01 and IGKV2-30*02) and heavy chain (Gene ID–V gene: IGHV1_69_2*01 and IGHV4-38-2*01) were used as the human frameworks.
  • the complementarity-determining regions (CDRs) of murine anti-huC5aR1 antibody light chain and heavy chain were grafted into the identified closest human frameworks respectively to generate humanized antibody clone.
  • antibody 10G1 and 1C2 were humanized by grafting the CDRs from the murine antibody V-regions onto human germline antibody V-region frameworks, the CDRs grafted from the donor to the acceptor sequence are as defined by Kabat (Kabat et al., 1987).
  • a number of framework residues from the murine V-regions that were found to be parts of V H -V L interacting interface or the framework residues acting as “Vernier” zone which may adjust CDR structure and fine-tune to fit to antigen (Foote et al., 1992) were also retained in the humanized sequence.
  • Example 5 In vitro Assays of Humanized Anti-C5aR1 Antibodies [0627] Generation of recombinant IgG versions of humanized anti-C5aR1 antibodies [0628] The full-length IgG versions of humanized C5aR1 antibodies were generated as described above. [0629] C5a Receptor binding assay: The binding of humanized anti-C5aR1 antibodies to huC5aR1-overexpressing cells was examined as described above in Example 2. EC50 values of the humanized anti-C5aR1 antibodies derived from 1C2 and 10G1 were summarized respectively in Table 9 and Table 10.
  • the EC 50 values of the exemplary humanized antibodies were also shown in Figure 2 and Figure 6.
  • the exemplary humanized antibody 1C2.35 exhibited comparable or even better binding activity to C5aR1 as compared to its corresponding chimeric antibody 1C2, and the humanization did not alter its binding function.
  • the exemplary humanized antibody 10G1.44 exhibited reduced binding activity as compared to its corresponding chimeric antibody.
  • Phagemid displaying monovalent Fab on the surface of M13 bacteriophage served as the library template for grafting.
  • the library DNA with homologous ends to linearized phagemid vector was generated through overlap PCR.
  • the phage library was generated according to established protocols and was around 7.1 ⁇ 10 8 transformants in size, as estimated by dilution plating. A number of bacterial colonies were sequenced to check the diversity of the library. [0639] Panning and screening of phage display library: Four to six affinity maturation panning rounds using the above library were carried out.
  • phages were pre- incubated with 2 ⁇ 10 6 Expi293 cells in PBS at RT for 30 min to deplete non-specific binders. Cells were pelleted at 2,000 g for 2 min and the unbound phage containing supernatant was collected and phage numbers were determined by OD.1 ⁇ 10 13 unbound phages were then added to 2 ⁇ 10 6 Expi293 cells overexpressing huC5aR1 that were labeled with carboxyfluorescein succinimidyl amino ester (CFSE). Cells were incubated with the phage for 10 min on ice.
  • CFSE carboxyfluorescein succinimidyl amino ester
  • the cells were pelleted at 2,000 g and washed 4-7 times (increasing in number at later panning rounds) with 1 ⁇ PBS to remove unbound phage. After washing, 8 ⁇ 10 6 unlabeled Expi293 cells overexpressing huC5aR1 were added to capture fast off-rate phage and the mixture was incubated for 30 min at RT. After incubation, the cells were pelleted at 2,000 g and washed 4 times with 1 ⁇ PBS and resuspended in 1 ml PBS. Cells were stained for bound phage using biotin-labeled anti-M13 phage protein for 30 min at RT.
  • IMQ imiquimod
  • Mice were subsequently treated with daily topical doses (62.5mg) of commercially available IMQ cream (5%; Si-Chuan Med-Shine Pharmaceutical, H20030128, Chengdu, Sichuan, China) for six days.
  • Naive group represents wild type mouse as control.
  • Body weight, ear thickness, dermal scaling and redness are scored daily (PASI score). Skin tissue is collected at day 6 and analyzed by histology for dermal thickening.
  • FIGS.8A-8D show the in vivo anti-autoimmune efficacy results of exemplary anti-C5aR1 antibody 1C2 in murine model of imiquimod-induced psoriasis.
  • FIG.8A shows the H&E staining results for skin thickness and scales from psoriatic skin lesions samples after treatment of exemplary anti-C5aR1 antibody 1C2 or reference antibody.
  • FIG.8B shows the epidermal thickness quantification result from psoriatic skin lesions samples after treatment of exemplary anti-C5aR1 antibody 1C2 or reference antibody.
  • FIG.8C shows the psoriasis area severity index (PASI) total score result of exemplary anti- C5aR1 antibody 1C2 or the reference antibody after IMQ treatment.
  • FIG.8D shows a schematic diagram of experimental protocol including prophylactic anti-C5aR1 antibody treatment, followed by disease induction by IMQ treatment and collection and recording of the parameters during and after the experiment.
  • the exemplary antibody 1C2 exhibited comparable reduction of skin thickness, scales and PASI total score from psoriatic skin lesions as compared to the reference Ab, demonstrating that the exemplary antibody 1C2 prevented inflammation and tissue destruction equally well compared to the reference Ab.
  • the exemplary anti-C5aR1 antibody 10G1 also exhibited prevention of inflammation and tissue destruction in murine model of imiquimod-induced psoriasis (data not shown).
  • Example 8 Anti-tumor therapy [0652] Subcutaneous Tumor Models: MC38 [0653] A summary of the subcutaneous tumor model studies was shown in Table 18 (below). TABLE 18: Summary of in vivo subcutaneous tumor study protocol [0654] Animals and husbandry: Female huC5aR1-Tg mice (7-9 weeks of age) (Biocytogen) were used in the studies. The animals were fed irradiated Harlan 2918.15 Rodent Diet and water ad libitum.
  • MC38 cells were obtained from ATCC and cultured according to manufacture protocols known in the field. The cells were suspended in Dulbecco’s Phosphate Buffered Saline (DPBS) at a concentration of 5 ⁇ 10 6 /ml.
  • DPBS Phosphate Buffered Saline
  • Test animals were sterilized at the implantation site with an alcohol prep pad and were implanted subcutaneously in 0.1 mL using a 25-gauge needle and 1 mL syringe.
  • Group 1 received IgG1 isotype control (synthesized in house) antibody, and group 2 received 1C2.35 antibody, group 3 received 10G1.44 antibody, group 4 received 10G1.44.1 antibody, group 5 received 10G1.44.6 antibody.

Abstract

The present application provides antibodies including antigen binding fragment thereof that specifically recognizing C5a anaphylatoxin chemotactic receptor 1 (C5aR1). Also provided are methods of making and using these antibodies.

Description

ANTIBODIES SPECIFICALLY RECOGNIZING C5aR1 AND USES THEREOF REFERENCE TO AN ELECTRONIC SEQUENCE LISTING [0001] The contents of the electronic sequence listing (C5aR1_seqlist_EN_20220811.xml; Size: 135KB; and Date of Creation: August 11, 2022) is herein incorporated by reference in its entirety. FIELD OF THE APPLICATION [0002] This application pertains to antibodies that specifically recognize C5a anaphylatoxin chemotactic receptor 1 (C5aR1), and methods of manufacture and uses thereof, including methods of treating inflammatory diseases, autoimmune disease, or cancers. BACKGROUND OF THE APPLICATION [0003] The complement system, which widely exist in the blood and tissue fluid and on the cell surface, consists of a tightly regulated network of proteins that play an important role in host defense and inflammation. Complement activation results in opsonization of pathogens and their removal by phagocytes, as well as cell lysis and thus is an important defense system in human body. [0004] C5a anaphylatoxin chemotactic receptor 1 (C5aR1, also known as CD88) is a member of the rhodopsin superfamily of G-protein-coupled receptor (GPCR) (Gerard NP et al., J Biol Chem 264: 1760-1766, 1989). C5aR, with its high affinity ligand C5a, is an essential part of the complement system, playing important role in eliciting the broad immune responses. The structure of C5aR1 conforms to the seven transmembrane receptor family and contains 4 extracellular domains, seven membrane-spanning helices, and 4 intracellular C domians (Dixon et al. Nature 326, 73-77, 1987; Findlay et al. Biochem. J.238, 625-642, 1986). C5aR is a classical G protein-coupled receptor that signals through Gαi and Gα16 which both are G-proteins. Activated C5aR has been shown to associate with two of the four mammalian β- arrestins (β-arrestin 1, 2), which have different dependencies on the phosphorylation status of the receptor. Upon agonist biding, C5aR undergoes rapid phosphorylation on the six serine residues present in the C-terminal region followed by desensitization and internalization. Serine residues in the C5aR C terminus were identified that control the intracellular trafficking of the C5aR-arrestin complex in response to C5a^^(Braun et al. J Biol Chem. 278:4277-4285, 2003). [0005] C5aR1 has been found to be expressed on various inflammatory cells and smooth muscle cells to promote an inflammatory reaction. It is also present on subsets of T cells and dendritic cells to regulate the adaptive immune response (Kemper et al. Nature Rev. Immunol. 7.9-18, 2007). C5a-C5aR interaction is required for the optimal oxidative burst and phagocytosis, which form the fundamental machinery in innate immunity for bacterial clearance. The binding of C5a ligand and its receptor C5aR thereof induces an inflammatory reaction by inducing cytokine and chemokine expression (Monsinjon et al. FASEB J 17:1003–1014, 2003.; Fukuoka et al. Clin Exp Immunol 131:248–253, 2003). C5a-C5aR interaction is also an essential step in neutrophil migration by causing adhesion molecule expression and inducing chemokine production (Riedemann et al. Immunity 19:193–202, 2003.). It has been reported that C5aR1 and its ligand C5a play a key role in initiating and maintaining several inflammatory responses by recruiting and activating neutrophils and monocytes in the lungs (Julien Carvelli et al. Nature 588, 146-150, 2020). In addition, C5a perturbs coagulation and fibrinolysis pathway, resulting in damaging intravascular coagulation (Muhlfelder et al. J Clin Invest 63:147–150, 1979.; Laudes et al. Am J Pathol 160:1867–1875, 2002.). In addition, it has been reported that activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene in cancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival (Cho Ms et al. Cell Rep.2014). [0006] Inhibition of C5a-C5aR interaction should reduce the acute inflammatory response mediated via C5a. The blockade of C5aR signal, thereby reducing of the inflammatory reaction, has also been researched. WO2003/062278A and WO2008/022390A disclose anti- C5aR1 antibodies and methods to obtain and use them. However, as an optimal therapeutic directed to a target in this pathway has yet to be commercialized, a significant unmet medical need exists [0007] Thus, there remains a need in the art for therapeutic antibodies that effectively inhibit or otherwise antagonize C5aR1, and related methods of treating diseases or conditions mediated through C5aR1, such as cancers, inflammatory diseases and autoimmune disease. [0008] The disclosures of all publications, patents, patent applications and published patent applications referred to herein are hereby incorporated herein by reference in their entirety. BRIEF SUMMARY OF THE APPLICATION [0009] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising SYWMN (SEQ ID NO: 1); an HC-CDR2 comprising RIDPX1X2X3X4TRYNQKFED (SEQ ID NO: 72), wherein X1 is G, R, S, or Y, X2 is D, R, or S, X3 is G or S, and X4 is E or G; and an HC-CDR3 comprising FVX1PX2GX3FX4Y (SEQ ID NO: 73), wherein X1 is I or W, X2 is L, M, Q, S, or V, X3 is A or G, and X4 is A or Q; and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSX1X2X3X4HSNGX5TYLH (SEQ ID NO: 74), wherein X1 is Q or R, X2 is Q or S, X3 is L or P, X4 is L or V, and X5 is N or Q; an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising X1QSTX2VPPT (SEQ ID NO: 75), wherein X1 is M or S, and X2 is F, H, L, R, V, or Y. [0010] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, or a variant thereof comprising up to about 3 amino acid substitutions; an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-15, or a variant thereof comprising up to about 3 amino acid substitutions; and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-31, or a variant thereof comprising up to about 3 amino acid substitutions; and a VL comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-44, or a variant thereof comprising up to about 3 amino acid substitutions; an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NO: 52, or a variant thereof comprising up to about 3 amino acid substitutions; and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-64, or a variant thereof comprising up to about 3 amino acid substitutions. [0011] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of the VH comprising the amino acid sequence of any one of SEQ ID NOs: 76-91; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of the VL comprising the amino acid sequence of any one of SEQ ID NOs: 104-120. [0012] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 76; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 104; (ii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 77; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 105; (iii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 78; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 106; (iv) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 79; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 107; (v) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 80; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 106; (vi) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 81; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 108; (vii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 82; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 109; (viii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 83; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 110; (ix) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 83; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 111; (x) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 84; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 112; (xi) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 85; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 113; (xii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 86; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 107; (xiii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 87; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 114; (xiv) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 88; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 115; (xv) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 89; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 116; (xvi) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 90; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 117; (xvii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 91; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 118; (xviii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 89; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 119; (xix) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 89; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 120. [0013] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (ii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (iii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (iv) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (v) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (vi) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (vii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to about 5 amino acid substitutions in the HC- CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC- CDR3 comprising the amino acid sequence of SEQ ID NO: 61, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (viii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (ix) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC- CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (x) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (xi) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (xii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (xiii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or a variant thereof comprising up to about 5 amino acid substitutions in the HC- CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC- CDR3 comprising the amino acid sequence of SEQ ID NO: 59, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [0014] In some embodiments, according to any one of the isolated anti-C5aR1 antibodies described above, the isolated anti-C5aR1 antibody comprises: a VH comprising the amino acid sequence of any one of SEQ ID NOs: 76-91, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 76-91; and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 104-120, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 104-120. [0015] In some embodiments, the isolated anti-C5aR1 antibody comprises: (i) a VH comprising the amino acid sequence of SEQ ID NO: 76, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 76; and a VL comprising the amino acid sequence of SEQ ID NO: 104, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 104; (ii) a VH comprising the amino acid sequence of SEQ ID NO: 77, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 77; and a VL comprising the amino acid sequence of SEQ ID NO: 105, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 105; (iii) a VH comprising the amino acid sequence of SEQ ID NO: 78, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; and a VL comprising the amino acid sequence of SEQ ID NO: 106, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 106; (iv) a VH comprising the amino acid sequence of SEQ ID NO: 79, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 79; and a VL comprising the amino acid sequence of SEQ ID NO: 107, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 107; (v) a VH comprising the amino acid sequence of SEQ ID NO: 80, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 80; and a VL comprising the amino acid sequence of SEQ ID NO: 106, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 106; (vi) a VH comprising the amino acid sequence of SEQ ID NO: 81, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 81; and a VL comprising the amino acid sequence of SEQ ID NO: 108, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 108; (vii) a VH comprising the amino acid sequence of SEQ ID NO: 82, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 82; and a VL comprising the amino acid sequence of SEQ ID NO: 109, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 109; (viii) a VH comprising the amino acid sequence of SEQ ID NO: 83, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 83; and a VL comprising the amino acid sequence of SEQ ID NO: 110, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 110; (ix) a VH comprising the amino acid sequence of SEQ ID NO: 83, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 83; and a VL comprising the amino acid sequence of SEQ ID NO: 111, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 111; (x) a VH comprising the amino acid sequence of SEQ ID NO: 84, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 84; and a VL comprising the amino acid sequence of SEQ ID NO: 112, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 112; (xi) a VH comprising the amino acid sequence of SEQ ID NO: 85, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 85; and a VL comprising the amino acid sequence of SEQ ID NO: 113, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 113; (xii) a VH comprising the amino acid sequence of SEQ ID NO: 86, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 86; and a VL comprising the amino acid sequence of SEQ ID NO: 107, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 107; (xiii) a VH comprising the amino acid sequence of SEQ ID NO: 87, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 87; and a VL comprising the amino acid sequence of SEQ ID NO: 114, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 114; (xiv) a VH comprising the amino acid sequence of SEQ ID NO: 88, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 88; and a VL comprising the amino acid sequence of SEQ ID NO: 115, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 115; (xv) a VH comprising the amino acid sequence of SEQ ID NO: 89, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 89; and a VL comprising the amino acid sequence of SEQ ID NO: 116, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 116; (xvi) a VH comprising the amino acid sequence of SEQ ID NO: 90, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 90; and a VL comprising the amino acid sequence of SEQ ID NO: 117, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 117; (xvii) a VH comprising the amino acid sequence of SEQ ID NO: 91, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 91; and a VL comprising the amino acid sequence of SEQ ID NO: 118, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 118; (xviii) a VH comprising the amino acid sequence of SEQ ID NO: 89, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 89; and a VL comprising the amino acid sequence of SEQ ID NO: 119, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 119; (xix) a VH comprising the amino acid sequence of SEQ ID NO: 89, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 89; and a VL comprising the amino acid sequence of SEQ ID NO: 120, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 120. [0016] In some embodiments ^there is provided an isolated anti-C5aR1 antibody comprising: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising SGYSWH (SEQ ID NO: 2); an HC-CDR2 comprising YIHSSGDTDYNPSLKR (SEQ ID NO: 16); and an HC-CDR3 comprising SIGDY (SEQ ID NO: 32); and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 45); an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising SQSTHVPWT (SEQ ID NO: 65). [0017] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, or a variant thereof comprising up to about 3 amino acid substitutions; an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, or a variant thereof comprising up to about 3 amino acid substitutions; and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant thereof comprising up to about 3 amino acid substitutions; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, or a variant thereof comprising up to about 3 amino acid substitutions; an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof comprising up to about 3 amino acid substitutions; and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 3 amino acid substitutions. [0018] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of the VH comprising the amino acid sequence of any one of SEQ ID NOs: 92-96; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of the VL comprising the amino acid sequence of any one of SEQ ID NOs: 121-127. [0019] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 92; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 121; (ii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 93; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 122; (iii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 93; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 123; (iv) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 93; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 124; (v) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 94; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 125; (vi) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 95; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 126; (vii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 96; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 127; (viii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 96; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 124; (ix) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 96; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 125; (x) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 96; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 126. [0020] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [0021] In some embodiments, according to any one of the isolated anti-C5aR1 antibodies described above, the isolated anti-C5aR1 antibody comprises: a VH comprising the amino acid sequence of any one of SEQ ID NOs: 92-96, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 92-96; and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 121-127, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 121-127. [0022] In some embodiments, the isolated anti-C5aR1 antibody comprises: (i) a VH comprising the amino acid sequence of SEQ ID NO: 92, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 92; and a VL comprising the amino acid sequence of SEQ ID NO: 121, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 121; (ii) a VH comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 93; and a VL comprising the amino acid sequence of SEQ ID NO: 122, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 122; (iii) a VH comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 93; and a VL comprising the amino acid sequence of SEQ ID NO: 123, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 123; (iv) a VH comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 93; and a VL comprising the amino acid sequence of SEQ ID NO: 124, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 124; (v) a VH comprising the amino acid sequence of SEQ ID NO: 94, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 94; and a VL comprising the amino acid sequence of SEQ ID NO: 125, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 125; (vi) a VH comprising the amino acid sequence of SEQ ID NO: 95, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 95; and a VL comprising the amino acid sequence of SEQ ID NO: 126, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 126; (vii) a VH comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 96; and a VL comprising the amino acid sequence of SEQ ID NO: 127, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 127; (viii) a VH comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 96; and a VL comprising the amino acid sequence of SEQ ID NO: 124, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 124; (ix) a VH comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 96; and a VL comprising the amino acid sequence of SEQ ID NO: 125, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 125; (x) a VH comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 96; and a VL comprising the amino acid sequence of SEQ ID NO: 126, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 126. [0023] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 97; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 128. [0024] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [0025] In some embodiments, according to any one of the isolated anti-C5aR1 antibodies described above, the isolated anti-C5aR1 antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 97, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 97; and a VL comprising the amino acid sequence of SEQ ID NO: 128, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 128. [0026] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 98; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 129. [0027] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [0028] In some embodiments, according to any one of the isolated anti-C5aR1 antibodies described above, the isolated anti-C5aR1 antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 98, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 98; and a VL comprising the amino acid sequence of SEQ ID NO: 129, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 129. [0029] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 99; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 130. [0030] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [0031] In some embodiments, according to any one of the isolated anti-C5aR1 antibodies described above, the isolated anti-C5aR1 antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 99, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 99; and a VL comprising the amino acid sequence of SEQ ID NO: 130, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 130. [0032] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 100; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 131. [0033] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [0034] In some embodiments, according to any one of the isolated anti-C5aR1 antibodies described above, the isolated anti-C5aR1 antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 100, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 100; and a VL comprising the amino acid sequence of SEQ ID NO: 131, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 131. [0035] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 101; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 132. [0036] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 48, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [0037] In some embodiments, according to any one of the isolated anti-C5aR1 antibodies described above, the isolated anti-C5aR1 antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 101, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 101; and a VL comprising the amino acid sequence of SEQ ID NO: 132, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 132. [0038] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 102; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 133. [0039] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [0040] In some embodiments, according to any one of the isolated anti-C5aR1 antibodies described above, the isolated anti-C5aR1 antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 102, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 102; and a VL comprising the amino acid sequence of SEQ ID NO: 133, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 133. [0041] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 103; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 134. [0042] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 50, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [0043] In some embodiments, according to any one of the isolated anti-C5aR1 antibodies described above, the isolated anti-C5aR1 antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 103; and a VL comprising the amino acid sequence of SEQ ID NO: 134, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 134. [0044] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 102; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 135. [0045] In some embodiments, there is provided an isolated anti-C5aR1 antibody comprising: (i) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [0046] In some embodiments, according to any one of the isolated anti-C5aR1 antibodies described above, the isolated anti-C5aR1 antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 102, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 102; and a VL comprising the amino acid sequence of SEQ ID NO: 135, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 135. [0047] In some embodiments, there is provided an isolated anti-C5aR1 antibody that specifically binds to the human C5aR1 with a Kd from about 0.1pM or 1nM. [0048] In some embodiments, there is provided an isolated anti-C5aR1 antibody that specifically binds to C5aR1 competitively with any one of the isolated anti-C5aR1 antibodies described above. In some embodiments, there is provided an isolated anti-C5aR1 antibody that specifically binds to the same epitope as any one of isolated anti-C5aR1 antibodies described above. [0049] In some embodiments according to any of the isolated anti-C5aR1 antibodies described above, the isolated anti-C5aR1 antibody comprises an Fc fragment. In some embodiments, the isolated anti-C5aR1 antibody is a full-length IgG antibody. In some embodiments, the isolated anti-C5aR1 antibody is a full-length IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the anti-C5aR1 antibody is a chimeric, human, or humanized antibody. In some embodiments, the anti-C5aR1 antibody is an antigen binding fragment selected from the group consisting of a Fab, a Fab', a F(ab)'2, a Fab'-SH, a single- chain Fv (scFv), an Fv fragment, a dAb, a Fd, a nanobody, a diabody, and a linear antibody. [0050] In some embodiments, there is provided isolated nucleic acid molecule(s) that encodes any one of the anti-C5aR1 antibodies described above. In some embodiments, there is provided a vector comprising any one of the nucleic acid molecules described above. In some embodiments, there is provided a host cell comprising any one of the anti-C5aR1 antibodies described above, any one of the nucleic acid molecules described above, or any one of the vectors described above. In some embodiments, there is provided a method of producing an anti-C5aR1 antibody, comprising: a) culturing any one of the host cells described above under conditions effective to express the anti-C5aR1 antibody; and b) obtaining the expressed anti-C5aR1 antibody from the host cell. [0051] In some embodiments, there is provided a method of treating a disease or condition in an individual in need thereof, comprising administering to the individual an effective amount of any one of the anti-C5aR1 antibodies described above. In some embodiments, there is provided the use of any one of the anti-C5aR1 antibodies described herein for the preparation of pharmaceutical compositions for treating a disease or condition in an individual in need. In some embodiments, provided is the use of any one of the anti-C5aR1 antibodies described above, or a pharmaceutical composition comprising any one of anti-C5aR1 antibodies described above in the manufacture of a medicament for treating a disease or condition. In some embodiments, the disease or condition is associated with C5aR1, comprising inflammatory diseases, autoimmune disease, or cancers or condition. In some embodiments, the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. [0052] Also provided are pharmaceutical compositions, kits and articles of manufacture comprising any one of the anti-C5aR1 antibodies described above. BRIEF DESCRIPTION OF THE DRAWINGS [0053] FIG.1A shows the binding affinity of exemplary hybridoma and chimeric anti-C5aR1 antibodies 10G1 and 1C2 to human C5aR1 as analyzed by FACS. FIG.1B shows the inhibition of C5aR1 function by exemplary hybridoma and chimeric anti-C5aR1 antibodies 10G1 and 1C2 as analyzed by C5aR1-TEV/β-Arrestin-Luc reporter assay^ [0054] FIGS.2A-2B show the binding affinity of an exemplary humanized anti-C5aR1 antibody 1C2.35 to human C5aR1as analyzed by FACS. [0055] FIG.3 shows the ligand blocking assay of exemplary humanized anti-C5aR1 antibody 1C2.35 that blocks C5a binding to C5aR1 as analyzed by FACS. [0056] FIGS.4A-4B show the inhibition of C5aR1 function by an exemplary humanized anti- C5aR1 antibodies 1C2.35 as analyzed by C5aR1-TEV/β-Arrestin-Luc reporter assay^ [0057] FIGS.5A-5B show the inhibition of C5a-induced upregulation of neutrophil CD11b by an exemplary humanized anti-C5aR1 antibody 1C2.35. [0058] FIGS.6A-6B show the binding affinity of an exemplary humanized anti-C5aR1 antibody 10G1.44 to human C5aR1 as analyzed by FACS. [0059] FIGS.7A-7B show the inhibition of C5a-induced upregulation of neutrophil CD11b by an exemplary humanized anti-C5aR1 antibody 10G1.44. [0060] FIGS.8A-8D show the in vivo anti-autoimmune efficacy results of exemplary anti- C5aR1 antibody 1C2 in murine model of imiquimod-induced psoriasis. FIG.8A shows the H&E staining results for skin thickness and scales from psoriatic skin lesions samples after treatment of exemplary anti-C5aR1 antibody 1C2 or reference antibody. FIG.8B shows the epidermal thickness quantification result from psoriatic skin lesions samples after treatment of exemplary anti-C5aR1 antibody 1C2 or reference antibody. FIG.8C shows the psoriasis area severity index (PASI) total score result of exemplary anti-C5aR1 antibody 1C2 or the reference antibody after IMQ treatment. FIG.8D shows a schematic diagram of experimental protocol including prophylactic anti-C5aR1 antibody treatment, followed by disease induction by IMQ treatment and collection and recording of the parameters during and after the experiment. DETAILED DESCRIPTION OF THE APPLICATION [0061] The present application in one aspect provides an isolated anti-C5aR1 antibody that specifically binds to human and/or cynomolgus monkey C5aR1. By using a combination of hybridoma technology, humanization of antibody, affinity maturation, selections on naïve scFv phage libraries and appropriately designed biochemical and biological assays, we have identified highly potent antibody molecules that bind to human C5aR1 and inhibit the action of human C5aR1 to its receptor. The results presented herein indicate that the present application antibodies bind C5aR1, compared with the known anti-C5aR1 antibody 7F3 developed by Novo Nordisk, now held by InnatePharma, which was described in US patent NO.8071096, and surprisingly are even more potent than clone 7F3 (hereinafter referred to as “reference antibody”) as demonstrated in a variety of biological assays. [0062] The anti-C5aR1 antibodies provided by the present application include, for example, full-length anti-C5aR1 antibodies, anti-C5aR1 scFvs, anti-C5aR1 Fc fusion proteins, multi- specific (such as bispecific) anti-C5aR1 antibodies, anti-C5aR1 immunoconjugates, and the like. [0063] In some embodiments, the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising SYWMN (SEQ ID NO: 1); an HC-CDR2 comprising RIDPX1X2X3X4TRYNQKFED (SEQ ID NO: 72), wherein X1 is G, R, S, or Y, X2 is D, R, or S, X3 is G or S, and X4 is E or G; and an HC-CDR3 comprising FVX1PX2GX3FX4Y (SEQ ID NO: 73), wherein X1 is I or W, X2 is L, M, Q, S, or V, X3 is A or G, and X4 is A or Q; and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSX1X2X3X4HSNGX5TYLH (SEQ ID NO: 74), wherein X1 is Q or R, X2 is Q or S, X3 is L or P, X4 is L or V, and X5 is N or Q; an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising X1QSTX2VPPT (SEQ ID NO: 75), wherein X1 is M or S, and X2 is F, H, L, R, V, or Y. [0064] In some embodiments, the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising SGYSWH (SEQ ID NO: 2); an HC-CDR2 comprising YIHSSGDTDYNPSLKR (SEQ ID NO: 16); and an HC-CDR3 comprising SIGDY (SEQ ID NO: 32); and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 45); an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising SQSTHVPWT (SEQ ID NO: 65). [0065] In some embodiments, the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising SGYSWH (SEQ ID NO: 2); an HC-CDR2 comprising YTHNSGDTNYSPSLKR (SEQ ID NO: 17); and an HC-CDR3 comprising SVGDY (SEQ ID NO: 33); and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 45); an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising SQSTHVPWT (SEQ ID NO: 65). [0066] In some embodiments, the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising NYWMN (SEQ ID NO: 3); an HC-CDR2 comprising RIDPSDSETRYNQKFKD (SEQ ID NO: 18); and an HC-CDR3 comprising YGWLRGYYAMDY (SEQ ID NO: 34); and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTHLH (SEQ ID NO: 46); an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising SQSTLVPLT (SEQ ID NO: 66). [0067] In some embodiments, the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising TGYSWH (SEQ ID NO: 4); an HC-CDR2 comprising YIHSSGRTDYNPSLKS (SEQ ID NO: 19); and an HC-CDR3 comprising SVGDY (SEQ ID NO: 33); and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 45); an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising SQSTHVPWT (SEQ ID NO: 65). [0068] In some embodiments, the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising GYYMH (SEQ ID NO: 5); an HC-CDR2 comprising RVYPYNGVTAYNQNFKD (SEQ ID NO: 20); and an HC-CDR3 comprising RGLRNYGDDPWFAY (SEQ ID NO: 35); and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RASSSVSYMH (SEQ ID NO: 47); an LC-CDR2 comprising ATSNLAS (SEQ ID NO: 53); and an LC-CDR3 comprising QQWSSNPPT (SEQ ID NO: 67). [0069] In some embodiments, the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising GSWMN (SEQ ID NO: 6); an HC-CDR2 comprising RIYPGDGNTKYSGKFKD (SEQ ID NO: 21); and an HC-CDR3 comprising DYPYYVDY (SEQ ID NO: 36); and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLENSNGNTYLN (SEQ ID NO: 48); an LC-CDR2 comprising RVSNRFS (SEQ ID NO: 54); and an LC-CDR3 comprising LQLTHVPPT (SEQ ID NO: 68). [0070] In some embodiments, the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising SYWMN (SEQ ID NO: 1); an HC-CDR2 comprising RIDPFDSETRYNQKFKD (SEQ ID NO: 22); and an HC-CDR3 comprising ITTGPWFAY (SEQ ID NO: 37); and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RASQDISNYLN (SEQ ID NO: 49); an LC-CDR2 comprising YTSRLHS (SEQ ID NO: 55); and an LC-CDR3 comprising QQGNTLPPT (SEQ ID NO: 69). [0071] In some embodiments, the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising SDYAWN (SEQ ID NO: 7); an HC-CDR2 comprising YISYSGDTSYNPSLKS (SEQ ID NO: 23); and an HC-CDR3 comprising AGRRGFDY (SEQ ID NO: 38); and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RASQSISNYLH (SEQ ID NO: 50); an LC-CDR2 comprising YASQSIS (SEQ ID NO: 56); and an LC-CDR3 comprising QQSNSWPIFT (SEQ ID NO: 70). [0072] In some embodiments, the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC- CDR) 1 comprising SYWMN (SEQ ID NO: 1); an HC-CDR2 comprising RIDPFDSETRYNQKFKD (SEQ ID NO: 22); and an HC-CDR3 comprising ITTGPWFAY (SEQ ID NO: 37); and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising SASQGISNYLN (SEQ ID NO: 51); an LC-CDR2 comprising YTSSLHS (SEQ ID NO: 57); and an LC-CDR3 comprising QQYSKLPPT (SEQ ID NO: 71). [0073] Also provided are nucleic acids encoding the anti-C5aR1 antibodies, compositions comprising the anti-C5aR1 antibodies, and methods of making and using the anti-C5aR1 antibodies. Definitions [0074] As used herein, "treatment" or "treating" is an approach for obtaining beneficial or desired results, including clinical results. For purposes of this application, beneficial or desired clinical results include, but are not limited to, one or more of the following: alleviating one or more symptoms resulting from the disease, diminishing the extent of the disease, stabilizing the disease (e.g., preventing or delaying the worsening of the disease), preventing or delaying the spread (e.g., metastasis) of the disease, preventing or delaying the recurrence of the disease, delaying or slowing the progression of the disease, ameliorating the disease state, providing a remission (partial or total) of the disease, decreasing the dose of one or more of other medications required to treat the disease, delaying the progression of the disease, increasing or improving the quality of life, increasing weight gain, and/or prolonging survival. Also encompassed by "treatment" is a reduction of pathological consequence of the disease (such as, for example, leukocyte infiltration of the skin or organs for cancer). The methods of the application contemplate any one or more of these aspects of treatment. [0075] The term "antibody" includes full-length antibodies and antigen-binding fragments thereof. A full-length antibody comprises two heavy chains and two light chains. The variable regions of the light and heavy chains are responsible for antigen binding. The variable regions in both chains generally contain three highly variable loops called the complementarity determining regions (CDRs) (light chain (LC) CDRs including LC-CDR1, LC-CDR2, and LC-CDR3, heavy chain (HC) CDRs including HC-CDR1, HC-CDR2, and HC-CDR3). CDR boundaries for the antibodies and antigen-binding fragments disclosed herein may be defined or identified by the conventions of Kabat, Chothia, or Al-Lazikani (Al- Lazikani 1997; Chothia 1985; Chothia 1987; Chothia 1989; Kabat 1987; Kabat 1991). The three CDRs of the heavy or light chains are interposed between flanking stretches known as framework regions (FRs), which are more highly conserved than the CDRs and form a scaffold to support the hypervariable loops. The constant regions of the heavy and light chains are not involved in antigen binding, but exhibit various effector functions. Antibodies are assigned to classes based on the amino acid sequence of the constant region of their heavy chain. The five major classes or isotypes of antibodies are IgA, IgD, IgE, IgG, and IgM, which are characterized by the presence of α, δ, ε, γ, and μ heavy chains, respectively. Several of the major antibody classes are divided into subclasses 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). [0076] The term "antigen-binding fragment" as used herein includes an antibody fragment including, for example, a diabody, a Fab, a Fab', a F(ab')2, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2, a bispecific dsFv (dsFv-dsFv'), a disulfide stabilized diabody (ds diabody), a single-chain Fv (scFv), an scFv dimer (bivalent diabody), a multispecific antibody formed from a portion of an antibody comprising one or more CDRs, a single domain antibody, a nanobody, a domain antibody, a bivalent domain antibody, or any other antibody fragments that bind to an antigen but do not comprise a complete antibody structure. An antigen-binding fragment also includes a fusion protein comprising the antibody fragment described above. An antigen-binding fragment is capable of binding to the same antigen to which the parent antibody or a parent antibody fragment (e.g., a parent scFv) binds. In some embodiments, an antigen-binding fragment may comprise one or more CDRs from a particular human antibody grafted to a framework region from one or more different human antibodies. [0077] The term "epitope" as used herein refers to the specific group of atoms or amino acids on an antigen to which an antibody or antibody moiety binds. Two antibodies or antibody moieties may bind the same epitope within an antigen if they exhibit competitive binding for the antigen. [0078] As used herein, a first antibody "competes" for binding to a target C5aR1 with a second antibody when the first antibody inhibits target C5aR1 binding of the second antibody by at least about 50% (such as at least about any of 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99%) in the presence of an equimolar concentration of the first antibody, or vice versa. A high throughput process for "binning" antibodies based upon their cross- competition is described in PCT Publication No. WO 03/48731. [0079] As used herein, the term "specifically binds", "specifically recognizing", or "is specific for" refers to measurable and reproducible interactions, such as binding between a target and an antibody that is determinative of the presence of the target in the presence of a heterogeneous population of molecules, including biological molecules. For example, an antibody that specifically recognizes a target (which can be an epitope) is an antibody that binds to this target with greater affinity, avidity, more readily, and/or with greater duration than its 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 that is at least about 10 times its binding affinity for other targets. [0080] An "isolated" anti-C5aR1 antibody as used herein refers to an anti-C5aR1 antibody that (1) is not associated with proteins found in nature, (2) is free of other proteins from the same source, (3) is expressed by a cell from a different species, or, (4) does not occur in nature. [0081] The term "isolated nucleic acid" as used herein is intended to mean a nucleic acid of genomic, cDNA, or synthetic origin or some combination thereof, which by virtue of its origin the "isolated nucleic acid" (1) is not associated with all or a portion of a polynucleotide in which the "isolated nucleic acid" is found in nature, (2) is operably linked to a polynucleotide which it is not linked to in nature, or (3) does not occur in nature as part of a larger sequence. [0082] As used herein, the term "CDR" or "complementarity determining region" is intended to mean the non-contiguous antigen combining sites found within the variable region of both heavy and light chain polypeptides. These particular regions have been described by Kabat et al., J. Biol. Chem.252:6609-6616 (1977); Kabat et al., U.S. Dept. 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., 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 M.P. et al., Dev. Comp. Immunol., 27: 55-77 (2003); and Honegger and Plückthun, J. Mol. Biol., 309:657-670 (2001), where the definitions include overlapping or subsets of amino acid residues when compared against each other. Nevertheless, application of either definition to refer to a CDR of an antibody or grafted antibodies or variants thereof is intended to be within the scope of the term as defined and used herein. The amino acid residues which encompass the CDRs as defined by each of the above cited references are set forth below in Table 1 as a comparison. CDR prediction algorithms and interfaces are known in the art, including, for example, 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 contents of the references cited in this paragraph are incorporated herein by reference in their entireties for use in the present application and for possible inclusion in one or more claims herein. TABLE 1: CDR DEFINITIONS
Figure imgf000027_0001
[0083] The term "chimeric antibody" refers to an antibody in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit a biological activity of this application (see U.S. Patent No.4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)). [0084] "Fv" is the minimum antibody fragment which contains a complete antigen- recognition and binding site. This fragment consists of a dimer of one heavy- and one light- chain variable region domain in tight, non-covalent association. From the folding of these two domains emanate six hypervariable loops (3 loops each from the heavy and light chain) that contribute the amino acid residues for antigen binding and confer antigen binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site. [0085] "Single-chain Fv", also abbreviated as "sFv" or "scFv", are antibody fragments that comprise the VH and VL antibody domains connected into a single polypeptide chain. In some embodiments, the scFv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the scFv to form the desired structure for antigen binding. For a review of scFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol.113, Rosenburg and Moore eds., Springer-Verlag, New York, pp.269-315 (1994). [0086] The term "diabodies" refers to small antibody fragments prepared by constructing scFv fragments (see preceding paragraph) typically with short linkers (such as about 5 to about 10 residues) between the VH and VL domains such that inter-chain but not intra-chain pairing of the V domains is achieved, resulting in a bivalent fragment, i.e., fragment having two antigen-binding sites. Bispecific diabodies are heterodimers of two "crossover" scFv fragments in which the VH and VL domains of the two antibodies are present on different polypeptide chains. Diabodies are described more fully in, for example, EP 404,097; WO 93/11161; and Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993). [0087] "Humanized" forms of non-human (e.g., rodent) antibodies are chimeric antibodies that contain minimal sequence derived from the non-human antibody. For the most part, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a hypervariable region (HVR) of the recipient are replaced by residues from a hypervariable region of a non-human species (donor antibody) such as mouse, rat, rabbit or non-human primate having the desired antibody specificity, affinity, and capability. In some instances, framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies can comprise residues that are not found in the recipient antibody or in the donor antibody. These modifications are made to further refine antibody performance. In general, the humanized antibody will comprise substantially at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the FRs are those of a human immunoglobulin sequence. The humanized antibody optionally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see 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). [0088] "Percent (%) amino acid sequence identity" or "homology" with respect to the polypeptide and antibody sequences identified herein is defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the polypeptide being compared, after aligning the sequences considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skilled in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), or MUSCLE software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full-length of the sequences being compared. For purposes herein, however, % amino acid sequence identity values are generated using the sequence comparison computer program MUSCLE (Edgar, R.C., Nucleic Acids Research 32(5):1792-1797, 2004; Edgar, R.C., BMC Bioinformatics 5(1):113, 2004). [0089] The terms "Fc receptor" or "FcR" are used to describe a receptor that binds to the Fc region of an antibody. In some embodiments, an FcR of this application is one that binds to an IgG antibody (a γ receptor) and includes receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternatively spliced forms of these receptors. FcγRII receptors include FcγRIIA (an "activating receptor") and FcγRIIB (an "inhibiting receptor"), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof. Activating receptor FcγRIIA contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. Inhibiting receptor FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain (see review M. in Daëron, Annu. Rev. Immunol.15:203-234 (1997)). The term includes allotypes, such as FcγRIIIA allotypes: FcγRIIIA-Phe158, FcγRIIIA-Val158, FcγRIIA-R131 and/or FcγRIIA-H131. FcRs are reviewed in Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991); Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J. Lab. Clin. Med. 126:330-41 (1995). Other FcRs, including those to be identified in the future, are encompassed by the term "FcR" herein. The term also includes the neonatal receptor, FcRn, which is responsible for the transfer of maternal IgGs to the fetus (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol.24:249 (1994)). [0090] The term "FcRn" refers to the neonatal Fc receptor (FcRn). FcRn is structurally similar to major histocompatibility complex (MHC) and consists of an α-chain noncovalently bound to β2-microglobulin. The multiple functions of the neonatal Fc receptor FcRn are reviewed in Ghetie and Ward (2000) Annu. Rev. Immunol.18, 739-766. FcRn plays a role in the passive delivery of immunoglobulin IgGs from mother to young and the regulation of serum IgG levels. FcRn can act as a salvage receptor, binding and transporting pinocytosed IgGs in intact form both within and across cells, and rescuing them from a default degradative pathway. [0091] The "CH1 domain" of a human IgG Fc region usually extends from about amino acid 118 to about amino acid 215 (EU numbering system). [0092] "Hinge region" is generally defined as stretching from Glu216 to Pro230 of human IgG1 (Burton, Molec. Immunol.22:161-206 (1985)). Hinge regions of other IgG isotypes may be aligned with the IgG1 sequence by placing the first and last cysteine residues forming inter-heavy chain S-S bonds in the same positions. [0093] The "CH2 domain" of a human IgG Fc region usually extends from about amino acid 231 to about amino acid 340. The CH2 domain is unique in that it is not closely paired with another domain. Rather, two N-linked branched carbohydrate chains are interposed between the two CH2 domains of an intact native IgG molecule. It has been speculated that the carbohydrate may provide a substitute for the domain-domain pairing and help stabilize the CH2 domain. Burton, Molec Immunol.22:161-206 (1985). [0094] The "CH3 domain" comprises the stretch of residues of C-terminal to a CH2 domain in an Fc region (i.e. from about amino acid residue 341 to the C-terminal end of an antibody sequence, typically at amino acid residue 446 or 447 of an IgG). [0095] A "functional Fc fragment" possesses an "effector function" of a native sequence Fc region. Exemplary "effector functions" include C1q binding; complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor; BCR), etc. Such effector functions generally require the Fc region to be combined with a binding domain (e.g., an antibody variable domain) and can be assessed using various assays known in the art. [0096] An antibody with a variant IgG Fc with "altered" FcR binding affinity or ADCC activity is one which has either enhanced or diminished FcR binding activity (e.g., FcγR or FcRn) and/or ADCC activity compared to a parent polypeptide or to a polypeptide comprising a native sequence Fc region. The variant Fc which "exhibits increased binding" to an FcR binds at least one FcR with higher affinity (e.g., lower apparent Kd or IC50 value) than the parent polypeptide or a native sequence IgG Fc. According to some embodiments, the improvement in binding compared to a parent polypeptide is about 3-fold, such as about any of 5, 10, 25, 50, 60, 100, 150, 200, or up to 500-fold, or about 25% to 1000% improvement in binding. The polypeptide variant which "exhibits decreased binding" to an FcR, binds at least one FcR with lower affinity (e.g., higher apparent Kd or IC50 value) than a parent polypeptide. The decrease in binding compared to a parent polypeptide may be about 40% or more decrease in binding. [0097] "Antibody-dependent cell-mediated cytotoxicity" or "ADCC" refers to a form of cytotoxicity in which secreted Ig bound to Fc receptors (FcRs) present on certain cytotoxic cells (e.g., Natural Killer (NK) cells, neutrophils, and macrophages) enable these cytotoxic effector cells to bind specifically to an antigen-bearing target cell and subsequently kill the target cell with cytotoxins. The antibodies "arm" the cytotoxic cells and are required for such killing. The primary cells for mediating ADCC, NK cells, express FcγRIII only, whereas monocytes express FcγRI, FcγRII and FcγRIII. FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991). To assess ADCC activity of a molecule of interest, an in vitro ADCC assay, such as that described in US Patent No.5,500,362 or 5,821,337 may be performed. Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and Natural Killer (NK) cells. Alternatively, or additionally, ADCC activity of the molecule of interest may be assessed in vivo, e.g., in an animal model such as that disclosed in Clynes et al. PNAS (USA) 95:652-656 (1998). [0098] The polypeptide comprising a variant Fc region which "exhibits increased ADCC" or mediates ADCC in the presence of human effector cells more effectively than a polypeptide having wild type IgG Fc or a parent polypeptide is one which in vitro or in vivo is substantially more effective at mediating ADCC, when the amounts of polypeptide with variant Fc region and the polypeptide with wild type Fc region (or the parent polypeptide) in the assay are essentially the same. Generally, such variants will be identified using any in vitro ADCC assay known in the art, such as assays or methods for determining ADCC activity, e.g., in an animal model etc. In some embodiments, the variant is from about 5-fold to about 100-fold, e.g. from about 25 to about 50-fold, more effective at mediating ADCC than the wild type Fc (or parent polypeptide). [0099] "Complement dependent cytotoxicity" or "CDC" refers to the lysis of a target cell 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 antibodies (of the appropriate subclass) which are bound to their cognate antigen. To assess complement activation, a CDC assay, e.g. as described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996), may be performed. Polypeptide variants with altered Fc region amino acid sequences and increased or decreased C1q binding capability are described in US patent No. 6,194,551B1 and WO99/51642. The contents of those patent publications are specifically incorporated herein by reference. See also, Idusogie et al. J. Immunol.164: 4178-4184 (2000). [00100] Unless otherwise specified, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. The phrase nucleotide sequence that encodes a protein or a RNA may also include introns to the extent that the nucleotide sequence encoding the protein may in some version contain an intron(s). [00101] The term "operably linked" refers to functional linkage between a regulatory sequence and a heterologous nucleic acid sequence resulting in expression of the latter. For example, a first nucleic acid sequence is operably linked with a second nucleic acid sequence when the first nucleic acid sequence is placed in a functional relationship with the second nucleic acid sequence. For instance, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Generally, operably linked DNA sequences are contiguous and, where necessary to join two protein coding regions, in the same reading frame. [00102] "Homologous" refers to the sequence similarity or sequence identity between two polypeptides or between two nucleic acid molecules. When a position in both of the two compared sequences is occupied by the same base or amino acid monomer subunit, e.g., if a position in each of two DNA molecules is occupied by adenine, then the molecules are homologous at that position. The percent of homology between two sequences is a function of the number of matching or homologous positions shared by the two sequences divided by the number of positions compared times 100. For example, if 6 of 10 of the positions in two sequences are matched or homologous then the two sequences are 60% homologous. By way of example, the DNA sequences ATTGCC and TATGGC share 50% homology. Generally, a comparison is made when two sequences are aligned to give maximum homology. [00103] An "effective amount" of an anti-C5aR1 antibody or composition as disclosed herein, is an amount sufficient to carry out a specifically stated purpose. An "effective amount" can be determined empirically and by known methods relating to the stated purpose. [00104] The term "therapeutically effective amount" refers to an amount of an anti- C5aR1 antibody or composition as disclosed herein, effective to "treat" a disease or disorder in an individual. In the case of cancer, the therapeutically effective amount of the anti-C5aR1 antibody or composition as disclosed herein can reduce the number of cancer cells; reduce the tumor size or weight; inhibit (i.e., slow to some extent and preferably stop) cancer cell infiltration into peripheral organs; inhibit (i.e., slow to some extent and preferably stop) tumor metastasis; inhibit, to some extent, tumor growth; and/or relieve to some extent one or more of the symptoms associated with the cancer. To the extent the anti-C5aR1 antibody or composition as disclosed herein can prevent growth and/or kill existing cancer cells, it can be cytostatic and/or cytotoxic. In some embodiments, the therapeutically effective amount is a growth inhibitory amount. In some embodiments, the therapeutically effective amount is an amount that extends the survival of a patient. In some embodiments, the therapeutically effective amount is an amount that improves progression free survival of a patient. [00105] As used herein, by "pharmaceutically acceptable" or "pharmacologically compatible" is meant a material that is not biological or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition administered to a patient without causing any significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained. Pharmaceutically acceptable carriers or excipients have preferably met the required standards of toxicological and manufacturing testing and/or are included on the Inactive Ingredient Guide prepared by the U.S. Food and Drug Administration. [00106] It is understood that embodiments of the application described herein include "consisting of" and/or "consisting essentially of" embodiments. [00107] Reference to "about" a value or parameter herein includes (and describes) variations that are directed to that value or parameter per se. For example, description referring to "about X" includes description of "X". [00108] As used herein, reference to "not" a value or parameter generally means and describes "other than" a value or parameter. For example, the method is not used to treat cancer of type X means the method is used to treat cancer of types other than X. [00109] As used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. Anti-C5aR1 antibodies [00110] In one aspect, the present application provides anti-C5aR1 antibodies that specifically bind to human and/or cynomolgus monkey C5aR1. Anti-C5aR1 antibodies include, but are not limited to, humanized antibodies, chimeric antibodies, mouse antibodies, human antibodies, and antibodies comprising the heavy chain and/or light chain CDRs discussed herein. In one aspect, the present application provides isolated antibodies that bind to C5aR1. Contemplated anti-C5aR1 antibodies include, for example, full-length anti-C5aR1 antibodies (e.g., full-length IgG1 or IgG4), anti-C5aR1 scFvs, anti-C5aR1 Fc fusion proteins, multi-specific (such as bispecific) anti-C5aR1 antibodies, anti-C5aR1 immunoconjugates, and the like. In some embodiments, the anti-C5aR1 antibody is a full-length antibody (e.g., full-length IgG1 or IgG4) or antigen-binding fragment thereof, which specifically binds to C5aR1. In some embodiments, the anti-C5aR1 antibody is a Fab, a Fab', a F(ab)'2, a Fab'-SH, a single-chain Fv (scFv), an Fv fragment, a dAb, a Fd,a nanobody, a diabody, or a linear antibody. In some embodiments, reference to an antibody that specifically binds to C5aR1 means that the antibody binds to C5aR1 with an affinity that is at least about 10 times (including for example at least about any one of 10, 102, 103, 104, 105, 106, or 107 times) more tightly than its binding affinity for a non-target. In some embodiments, the non-target is an antigen that is not C5aR1. Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence activated cell sorting (FACS) analysis, or radioimmunoprecipitation assay (RIA). Kd can be determined by methods known in the art, such as surface plasmon resonance (SPR) assay or biolayer interferometry (BLI). [00111] Although anti-C5aR1 antibodies containing human sequences (e.g., human heavy and light chain variable domain sequences comprising human CDR sequences) are extensively discussed herein, non-human anti-C5aR1 antibodies are also contemplated. In some embodiments, non-human anti-C5aR1 antibodies comprise human CDR sequences from an anti-C5aR1 antibody as described herein and non-human framework sequences. Non-human framework sequences include, in some embodiments, any sequence that can be used for generating synthetic heavy and/or light chain variable domains using one or more human CDR sequences as described herein, including, e.g., mammals, e.g., mouse, rat, rabbit, pig, bovine (e.g., cow, bull, buffalo), deer, sheep, goat, chicken, cat, dog, ferret, primate (e.g., marmoset, rhesus monkey), etc. In some embodiments, a non-human anti-C5aR1 antibody includes an anti-C5aR1 antibody generated by grafting one or more human CDR sequences as described herein onto a non-human framework sequence (e.g., a mouse or chicken framework sequence). [00112] The complete amino acid sequence of an exemplary native human C5aR1 comprises or consists of the amino acid sequence of SEQ ID NO: 140. The complete amino acid sequence of an exemplary native musculus C5aR1 comprises or consists of the amino acid sequence of SEQ ID NO: 141. The complete amino acid sequence of an exemplary native cynomolgus monkey C5aR1 comprises or consists of the amino acid sequence of SEQ ID NO: 142. [00113] In some embodiments, the anti-C5aR1 antibody described herein specifically recognizes an epitope within human C5aR1. In some embodiments, the anti-C5aR1 antibody cross-reacts with C5aR1 from species other than human. In some embodiments, the anti- C5aR1 antibody is completely specific for human C5aR1 and does not exhibit cross- reactivity with C5aR1s from other non-human species. [00114] In some embodiments, the anti-C5aR1 antibody cross-reacts with at least one allelic variant of the C5aR1 protein (or fragments thereof). In some embodiments, the allelic variant has up to about 30 (such as about any of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30) amino acid substitutions (such as a conservative substitution) when compared to the naturally occurring C5aR1 (or fragments thereof). In some embodiments, the anti-C5aR1 antibody does not cross-react with any allelic variants of the C5aR1 protein (or fragments thereof). [00115] In some embodiments, the anti-C5aR1 antibody cross-reacts with at least one interspecies variant of the C5aR1 protein. In some embodiments, for example, the C5aR1 protein (or fragments thereof) is human C5aR1 and the interspecies variant of the C5aR1 protein (or fragments thereof) is a cynomolgus monkey variant thereof. In some embodiments, the anti-C5aR1 antibody does not cross-react with any interspecies variants of the C5aR1 protein. [00116] In some embodiments, according to any of the anti-C5aR1 antibodies described herein, the anti-C5aR1 antibody comprises an antibody heavy chain constant region and an antibody light chain constant region. In some embodiments, the anti-C5aR1 antibody comprises an IgG1 heavy chain constant region. In some embodiments, the anti-C5aR1 antibody comprises an IgG2 heavy chain constant region. In some embodiments, the anti- C5aR1 antibody comprises an IgG3 heavy chain constant region. In some embodiments, the anti-C5aR1 antibody comprises an IgG4 heavy chain constant region. In some embodiments, the heavy chain constant region comprises (including consisting of or consisting essentially of) the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises (including consisting of or consisting essentially of) the amino acid sequence of SEQ ID NO: 137. In some embodiments, the anti-C5aR1 antibody comprises a kappa light chain constant region. In some embodiments, the light chain constant region comprises (including consisting of or consisting essentially of) the amino acid sequence of SEQ ID NO: 138. In some embodiments, the anti-C5aR1 antibody comprises a lambda light chain constant region. In some embodiments, the light chain constant region comprises (including consisting of or consisting essentially of) the amino acid sequence of SEQ ID NO: 139. In some embodiments, the anti-C5aR1 antibody comprises an antibody heavy chain variable domain and an antibody light chain variable domain. [00117] In some embodiments, the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising SYWMN (SEQ ID NO: 1); an HC-CDR2 comprising RIDPX1X2X3X4TRYNQKFED (SEQ ID NO: 72), wherein X1 is G, R, S, or Y, X2 is D, R, or S, X3 is G or S, and X4 is E or G; and an HC-CDR3 comprising FVX1PX2GX3FX4Y (SEQ ID NO: 73), wherein X1 is I or W, X2 is L, M, Q, S, or V, X3 is A or G, and X4 is A or Q; and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSX1X2X3X4HSNGX5TYLH (SEQ ID NO: 74), wherein X1 is Q or R, X2 is Q or S, X3 is L or P, X4 is L or V, and X5 is N or Q; an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising X1QSTX2VPPT (SEQ ID NO: 75), wherein X1 is M or S, and X2 is F, H, L, R, V, or Y [00118] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC- CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-15, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-31, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions. [00119] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-15, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-31. [00120] In some embodiments, the anti-C5aR1 antibody comprises a VL comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-44, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-64, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions. [00121] In some embodiments, the anti-C5aR1 antibody comprises a VL comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-44, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-64. [00122] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC- CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-15, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-31, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions; and a VL comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-44, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-64, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions. [00123] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-15, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-31; and a VL comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-44, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-64. [00124] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00125] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. [00126] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00127] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. [00128] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00129] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. [00130] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00131] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. [00132] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00133] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59. [00134] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00135] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60. [00136] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00137] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61. [00138] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00139] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61. [00140] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00141] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62. [00142] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00143] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63. [00144] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00145] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. [00146] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00147] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64. [00148] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00149] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59. [00150] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of any one of SEQ ID NOs: 76-91; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of the VL comprising the amino acid sequence of any one of SEQ ID NOs: 104- 120. [00151] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 76, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 104. [00152] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 77, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 105. [00153] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 78, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 106. [00154] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 79, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 107. [00155] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 80, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 106. [00156] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 81, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 108. [00157] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 82, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 109. [00158] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 83, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 110. [00159] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 83, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 111. [00160] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 84, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 112. [00161] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 85, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 113. [00162] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 86, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 107. [00163] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 87, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 114. [00164] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 88, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 115. [00165] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 89, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 116. [00166] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 90, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 117. [00167] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 91, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 118. [00168] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 89, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 119. [00169] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 89, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 120. [00170] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of any one of SEQ ID NOs: 76-91, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 104-120, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of any one of SEQ ID NOs: 76-91, and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 104-120. [00171] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 76, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 104, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 76 and a VL comprising the amino acid sequence of SEQ ID NO: 104. [00172] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 77, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 105, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 77 and a VL comprising the amino acid sequence of SEQ ID NO: 105. [00173] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 78, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 106, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 78 and a VL comprising the amino acid sequence of SEQ ID NO: 106. [00174] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 79, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 107, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 79 and a VL comprising the amino acid sequence of SEQ ID NO: 107. [00175] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 80, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 106, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 80 and a VL comprising the amino acid sequence of SEQ ID NO: 106. [00176] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 81, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 108, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 81 and a VL comprising the amino acid sequence of SEQ ID NO: 108. [00177] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 82, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 109, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 82 and a VL comprising the amino acid sequence of SEQ ID NO: 109. [00178] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 83, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 110, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 83 and a VL comprising the amino acid sequence of SEQ ID NO: 110. [00179] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 83, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 111, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 83 and a VL comprising the amino acid sequence of SEQ ID NO: 111. [00180] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 84, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 112, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 84 and a VL comprising the amino acid sequence of SEQ ID NO: 112. [00181] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 85, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 113, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 85 and a VL comprising the amino acid sequence of SEQ ID NO: 113. [00182] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 86, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 107, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 86 and a VL comprising the amino acid sequence of SEQ ID NO: 107. [00183] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 87, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 114, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 87 and a VL comprising the amino acid sequence of SEQ ID NO: 114. [00184] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 88, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 115, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 88 and a VL comprising the amino acid sequence of SEQ ID NO: 115. [00185] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 89, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 116, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 89 and a VL comprising the amino acid sequence of SEQ ID NO: 116. [00186] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 90, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 117, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 90 and a VL comprising the amino acid sequence of SEQ ID NO: 117. [00187] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 91, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 118, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 91 and a VL comprising the amino acid sequence of SEQ ID NO: 118. [00188] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 89, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 119, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 89 and a VL comprising the amino acid sequence of SEQ ID NO: 119. [00189] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 89, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 120, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 89 and a VL comprising the amino acid sequence of SEQ ID NO: 120. [00190] In some embodiments, the isolated anti-C5aR1 antibody comprises: a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising SGYSWH (SEQ ID NO: 2); an HC-CDR2 comprising YIHSSGDTDYNPSLKR (SEQ ID NO: 16); and an HC-CDR3 comprising SIGDY (SEQ ID NO: 32); and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 45); an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising SQSTHVPWT (SEQ ID NO: 65) [00191] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC- CDR2 comprising the amino acid sequence of SEQ ID NO: 16, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions. [00192] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32. [00193] In some embodiments, the anti-C5aR1 antibody comprises a VL comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions. [00194] In some embodiments, the anti-C5aR1 antibody comprises a VL comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65. [00195] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC- CDR2 comprising the amino acid sequence of SEQ ID NO: 16, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions; and a VL comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions. [00196] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32; and a VL comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65. [00197] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00198] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65. [00199] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of any one of SEQ ID NOs: 92-96; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of the VL comprising the amino acid sequence of any one of SEQ ID NOs: 121- 127. [00200] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 92, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 121. [00201] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 93, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 122. [00202] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 93, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 123. [00203] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 93, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 124. [00204] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 94, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 125. [00205] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 95, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 126. [00206] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 96, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 127. [00207] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 96, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 124. [00208] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 96, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 125. [00209] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 96, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 126. [00210] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of any one of SEQ ID NOs: 92-96, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 121-127, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of any one of SEQ ID NOs: 92-96, and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 121-127. [00211] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 92, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 121, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 92 and a VL comprising the amino acid sequence of SEQ ID NO: 121. [00212] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 122, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 93 and a VL comprising the amino acid sequence of SEQ ID NO: 122. [00213] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 123, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 93 and a VL comprising the amino acid sequence of SEQ ID NO: 123. [00214] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 124, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 93 and a VL comprising the amino acid sequence of SEQ ID NO: 124. [00215] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 94, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 125, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 94 and a VL comprising the amino acid sequence of SEQ ID NO: 125. [00216] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 95, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 126, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 95 and a VL comprising the amino acid sequence of SEQ ID NO: 126. [00217] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 127, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 96 and a VL comprising the amino acid sequence of SEQ ID NO: 127. [00218] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 124, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 96 and a VL comprising the amino acid sequence of SEQ ID NO: 124. [00219] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 125, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 96 and a VL comprising the amino acid sequence of SEQ ID NO: 125. [00220] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 126, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 96 and a VL comprising the amino acid sequence of SEQ ID NO: 126. [00221] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00222] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65. [00223] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 97, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 128. [00224] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 97, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 128, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 97 and a VL comprising the amino acid sequence of SEQ ID NO: 128. [00225] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00226] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66. [00227] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 98, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 129. [00228] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 98, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 129, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 98 and a VL comprising the amino acid sequence of SEQ ID NO: 129. [00229] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00230] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65. [00231] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 99, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 130. [00232] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 99, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 130, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 99 and a VL comprising the amino acid sequence of SEQ ID NO: 130. [00233] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00234] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67. [00235] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 100, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 131. [00236] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 100, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 131, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 100 and a VL comprising the amino acid sequence of SEQ ID NO: 131. [00237] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 48, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00238] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 48, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68. [00239] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 101, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 132. [00240] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 101, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 132, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 101 and a VL comprising the amino acid sequence of SEQ ID NO: 132. [00241] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00242] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69. [00243] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 102, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 133. [00244] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 102, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 133, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 102 and a VL comprising the amino acid sequence of SEQ ID NO: 133. [00245] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 50, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00246] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 50, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70. [00247] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 103, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 134. [00248] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 134, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 103 and a VL comprising the amino acid sequence of SEQ ID NO: 134. [00249] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs. [00250] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71. [00251] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2 and an HC-CDR3 of the VH comprising the amino acid sequence of SEQ ID NO: 102, and a VL comprising an LC-CDR1, an LC-CDR2 and an LC-CDR3 of the VL comprising the amino acid sequence of SEQ ID NO: 135. [00252] In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 102, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a VL comprising the amino acid sequence of SEQ ID NO: 135, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the anti-C5aR1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 102 and a VL comprising the amino acid sequence of SEQ ID NO: 135. [00253] In some embodiments, the amino acid substitutions described above are limited to "exemplary substitutions" shown in Table 4 of this application. In some embodiments, the amino acid substitutions are limited to “preferred substitutions” shown in Table 4 of this application. [00254] In some embodiments, functional epitopes can be mapped by combinatorial alanine scanning. In this process, a combinatorial alanine-scanning strategy can be used to identify amino acids in the C5aR1 protein that are necessary for interaction with C5aR1 antibodies. In some embodiments, the epitope is conformational and crystal structure of anti- C5aR1 antibodies bound to C5aR1 may be employed to identify the epitopes. [00255] In some embodiments, the present application provides antibodies which compete with any one of the C5aR1 antibodies described herein for binding to C5aR1. In some embodiments, the present application provides antibodies which compete with any one of the anti-C5aR1 antibodies provided herein for binding to an epitope on the C5aR1. In some embodiments, an anti-C5aR1 antibody is provided that binds to the same epitope as an anti-C5aR1 antibody comprising a VH comprising the amino acid sequence of any one of SEQ ID NOs: 76-103, and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 104-135. In some embodiments, an anti-C5aR1 antibody is provided that specifically binds to C5aR1 competitively with an anti-C5aR1 antibody comprising a VH comprising the amino acid sequence of any one of SEQ ID NOs: 76-103 and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 104-135. [00256] In some embodiments, competition assays may be used to identify a monoclonal antibody that competes with an anti-C5aR1 antibody described herein for binding to C5aR1. Competition assays can be used to determine whether two antibodies bind to the same epitope by recognizing identical or sterically overlapping epitopes or one antibody competitively inhibits binding of another antibody to the antigen. In certain embodiments, such a competing antibody binds to the same epitope that is bound by an antibody described herein. Exemplary competition assays include, but are not limited to, routine assays such as those provided in Harlow and Lane (1988) Antibodies: A Laboratory Manual ch.14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.). Detailed exemplary methods for mapping an epitope to which an antibody binds are provided in Morris (1996) "Epitope Mapping Protocols", in Methods in Molecular Biology vol.66 (Humana Press, Totowa, N.J.). In some embodiments, two antibodies are said to bind to the same epitope if each blocks binding of the other by 50% or more. In some embodiments, the antibody that competes with an anti-C5aR1 antibody described herein is a chimeric, humanized or human antibody. [00257] Exemplary anti-C5aR1 antibody sequences are shown in Tables 2 and 3, wherein the CDR numbering is according to the EU index of Kabat. Those skilled in the art will recognize that many algorithms are known for prediction of CDR positions and for delimitation of antibody heavy chain and light chain variable regions. Anti-C5aR1 antibodies comprising CDRs, VH and/or VL sequences from antibodies described herein, but based on prediction algorithms other than those exemplified in the tables below, are within the scope of this invention. Table 2A. Exemplary anti-C5aR1 antibody CDR sequences.
Figure imgf000064_0001
Figure imgf000065_0001
Table 2B. Exemplary anti-C5aR1 antibody CDR sequences.
Figure imgf000065_0002
Figure imgf000066_0001
Figure imgf000066_0002
Figure imgf000067_0001
Table 2C. Exemplary anti-C5aR1 antibody CDR sequences.
Figure imgf000068_0001
Figure imgf000069_0001
Table 3A. Exemplary sequences.
Figure imgf000069_0002
Figure imgf000070_0001
Figure imgf000071_0001
Table 3B. Exemplary sequences.
Figure imgf000071_0002
Figure imgf000071_0003
Figure imgf000072_0001
Figure imgf000073_0002
Table 3C. Exemplary sequences.
Figure imgf000073_0001
Figure imgf000074_0001
C5aR1 [00258] The complement system consists of a tightly regulated network of proteins that play an important role in host defense and inflammation. Complement activation is known to occur through three different pathways: alternate, classical and lectin pathways involving proteins that mostly exist as inactive zymogens that are then sequentially cleaved and activated. All the complement pathways converge at C3 which is the most abundant complement protein found in blood, resulting in the formation of the activation products, C3a, C3b, C5a and the membrane attack complex (C5b-9). Upon activation, proteolytic products of complement activation are recognized by specific receptors on cell surfaced that control cellular function. [00259] C5a anaphylatoxin chemotactic receptor 1 (C5aR1) is one of the two high affinity receptors for the ligand, C5a. It has been reported that the second and third extracellular loops (ECLs) of C5aR1 were essential for ligand binding (Pease et al.1994.). C5aR1 is a member of GPCR and couples to a wide range of G proteins such as Gαi2 (Sheth et al.1991; Skokowa et al.,2005) which is a pertussis toxin (PT)-sensitive G protein, and Gα16, a PT-insensitive G protein (Monk and Partridge, 1993). Activated C5aR1 has also been shown to associate with two of the four mammalian β-arrestins (β-arrestin 1, 2) which have different dependencies on the phosphorylation status of the receptor (Braun et al., 2003). The human C5aR1 binds C5a with a Kd of 1nM but has an affinity for C5a desArg that is 10- 100 folds lower. C5a has a short half-life in serum as the C-terminal arginine is quickly cleaved by carboxypeptidase N to form C5a desArg, which binds to C5aR1 with reduced affinity and displays biased signaling. C5a desArg, unlike C5a, does not signal the Gα pathway and does not stimulate granulocyte release. However, C5a desArg does stimulate neutrophil chemotaxis, so it is interest to also block C5a desArg binding to prevent neutrophil migration to the site of inflammation (Eric Wagner et al., Nature Rev, 2010). [00260] C5aR1 has been found to be expressed on various inflammatory cells and smooth muscle cells to promote an inflammatory reaction. It is also present on subsets of T cells and dendritic cells to regulate the adaptive immune response (Kemper et al. Nature Rev. Immunol.7.9-18, 2007). C5a-C5aR interaction is required for the optimal oxidative burst and phagocytosis, which form the fundamental machinery in innate immunity for bacterial clearance. The binding of C5a ligand and its receptor C5aR thereof induces an inflammatory reaction by inducing cytokine and chemokine expression (Monsinjon et al. FASEB J 17:1003–1014, 2003.; Fukuoka et al. Clin Exp Immunol 131:248–253, 2003). C5a-C5aR interaction is also an essential step in neutrophil migration by causing adhesion molecule expression and inducing chemokine production (Riedemann et al. Immunity 19:193–202, 2003.). It has been reported that C5aR1 and its ligand C5a play a key role in initiating and maintaining several inflammatory responses by recruiting and activating neutrophils and monocytes in the lungs (Julien Carvelli et al. Nature 588, 146-150, 2020). In addition, C5a perturbs coagulation and fibrinolysis pathway, resulting in damaging intravascular coagulation (Muhlfelder et al. J Clin Invest 63:147–150, 1979.; Laudes et al. Am J Pathol 160:1867–1875, 2002.). [00261] In addition to the correlation between interaction C5aR and C5a with inflammatory and autoimmune diseases, some researches have been reported to identify the underlying mechanisms by which C5a stimulates tumor growth. Mariewski et al. described that complement production by cancer cells altered immune cells infiltrating into tumors (increased myeloid-derived suppressor cells and reduced cytotoxic T cells) (Mariewski et al., Nat Immunol, 2008). Otherwise, Cho Ms et al. have identified a prominent role for tumor- dereived complement production and activation in ovarian cancer and progression. They found that knockdown of C3aR and C5aR in cancer cells reduced the size of induced tumors in mice. C5aR and C3aR agonists increased proliferation, migration and invasion of ovarian cancer cells, and C5aR and C3aR antagonists decreased proliferation of these cells. Anaphylatoxin receptors signal through the PI3/AKT pathway in cancer cells, and the proliferative effect of C5aR and C3aR stimulation could be eliminated by AKT silencing (Cho Ms et al., Cell Rep, 2014). These findings have significant implications for innovative therapeutic and biomarkers strategies for ovarian and other cancers (Hill et al., 2010). C5a [00262] The ligand C5a is an activated product of the complement system, and elicits the broadest immune responses. C5a is produced in serum as one of the core effector components of the complement response and is one of best described and most potent proinflammatory mediators derived from the complement systems. One of the two high affinity receptors for the ligand C5a, called C5a anaphylatoxin chemotactic receptor 1 (C5aR1, also known as CD88), is a member of the rhodopsin superfamily of G-protein- coupled receptor (GPCR) (Gerard NP et al., J Biol Chem 264: 1760-1766, 1989). The binding of C5a ligand and its receptor C5aR thereof induces an inflammatory reaction by inducing cytokine and chemokine expression (Monsinjon et al. FASEB J 17:1003–1014, 2003.; Fukuoka et al. Clin Exp Immunol 131:248–253, 2003). The other receptor, G protein-coupled receptor 77 (GPR77, also known as C5L2), recognized C5a and its inactivated form, C5a desArg, but seems to downregulate rather than promote an inflammary responses (Monk et al. Br, J. Pharmacol, 152,429-448, 2007). C5a has been shown to be spasmogenic, chemotactic to increase vascular permeability and induce the release pharmacologically active mediators from numerous cell types. It has also been shown to directly or indirectly induce cytokine release from macrophages and to augment humoral- and cell-mediated immune responses in vitro (Shin et al., Science 162:361, 1968; Schorlemmer, et al., Nature 261:48, 1976.). Full-length anti-C5aR1 antibody [00263] The anti-C5aR1 antibody in some embodiments is a full-length anti-C5aR1 antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgA, IgD, IgE, IgG, or IgM. In some embodiments, the full-length anti-C5aR1 antibody comprises IgG constant domains, such as constant domains of any one of IgG1, IgG2, IgG3, and IgG4 including variants thereof. In some embodiments, the full-length anti-C5aR1 antibody comprises a lambda light chain constant region. In some embodiments, the full-length anti- C5aR1 antibody comprises a kappa light chain constant region. In some embodiments, the full-length anti-C5aR1 antibody is a full-length human anti-C5aR1 antibody. In some embodiments, the full-length anti-C5aR1 antibody comprises an Fc sequence of a mouse immunoglobulin. In some embodiments, the full-length anti-C5aR1 antibody comprises an Fc sequence that has been altered or otherwise changed so that it has enhanced antibody dependent cellular cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC) effector function. [00264] Thus, for example, in some embodiments, there is provided a full-length anti- C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody specifically binds to C5aR1. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00265] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG2 constant domains, wherein the anti-C5aR1 antibody specifically binds to C5aR1. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00266] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG3 constant domains, wherein the anti-C5aR1 antibody specifically binds to C5aR1. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00267] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody specifically binds to C5aR1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00268] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-51, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 52-57, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-71, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00269] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG2 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-51, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 52-57, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-71, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00270] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG3 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-51, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 52-57, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-71, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00271] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-51, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 52-57, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-71, or a variant thereof comprising up to about 3 (such as about any of 1, 2, or 3) amino acid substitutions. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00272] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38, or a variant thereof comprising up to about 5 (such as about any of 1, 2, 3, 4, or 5) amino acid substitutions in the HC-CDR sequences; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-51, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 52-57, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-71, or a variant thereof comprising up to about 5 (such as about any of 1, 2, 3, 4, or 5) amino acid substitutions in the LC-CDR sequences. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00273] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38, or a variant thereof comprising up to about 5 (such as about any of 1, 2, 3, 4, or 5) amino acid substitutions in the HC-CDR sequences; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-51, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 52-57, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-71, or a variant thereof comprising up to about 5 (such as about any of 1, 2, 3, 4, or 5) amino acid substitutions in the LC-CDR sequences. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00274] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-51, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 52-57, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-71. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00275] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-7, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-23, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-38; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-51, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 52-57, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-71. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00276] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00277] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00278] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00279] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00280] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 28; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00281] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00282] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00283] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00284] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 30; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00285] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00286] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00287] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00288] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00289] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 32; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00290] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00291] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00292] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00293] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00294] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 36; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 48, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00295] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00296] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 38; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 50, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00297] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00298] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 24; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00299] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00300] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00301] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00302] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 28; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00303] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00304] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00305] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 26; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00306] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 30; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00307] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00308] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00309] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00310] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 27; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00311] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 32; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00312] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00313] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00314] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00315] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00316] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 36; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 48, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00317] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00318] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 38; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 50, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00319] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a) a heavy chain variable domain comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC- CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and b) a light chain variable domain comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00320] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 76- 103, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a light chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 104-135, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00321] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG2 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 76- 103, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a light chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 104-135, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00322] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG3 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 76- 103, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a light chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 104-135, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00323] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 76- 103, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity, and a light chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 104-135, or a variant thereof having at least about 80% (such as at least about any of 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00324] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 76- 103, and a light chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 104-135. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00325] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 76- 103, and a light chain variable domain comprising the amino acid sequence of any one of SEQ ID NOs: 104-135. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00326] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 76 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 104. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00327] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 77 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 105. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00328] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 78 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 106. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00329] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 79 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 107. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00330] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 80 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 106. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00331] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 81 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 108. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00332] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 82 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 109. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00333] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 83 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 110. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00334] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 83 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 111. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00335] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 84 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00336] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 85 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00337] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 86 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 107. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00338] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 87 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 114. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00339] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 88 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 115. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00340] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 89 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 116. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00341] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 90 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 117. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00342] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 91 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 118. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00343] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 89 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 119. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00344] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 89 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 120. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00345] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 92 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 121. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00346] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 93 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 122. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00347] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 93 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 123. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00348] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 93 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 124. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00349] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 94 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 125. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00350] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 95 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 126. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00351] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 127. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00352] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 124. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00353] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 125. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00354] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 126. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00355] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 97 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 128. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00356] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 98 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 129. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00357] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 99 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 130. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00358] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 100 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 131. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00359] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 101 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 132. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00360] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 102 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 133. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00361] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 103 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 134. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00362] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG1 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 102 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 135. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00363] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 76 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 104. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00364] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 77 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 105. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00365] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 78 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 106. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00366] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 79 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 107. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00367] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 80 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 106. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00368] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 81 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 108. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00369] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 82 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 109. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00370] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 83 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 110. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00371] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 83 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 111. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00372] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 84 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00373] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 85 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00374] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 86 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 107. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00375] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 87 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 114. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00376] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 88 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 115. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00377] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 89 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 116. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00378] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 90 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 117. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00379] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 91 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 118. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00380] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 89 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 119. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00381] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 89 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 120. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00382] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 92 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 121. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00383] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 93 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 122. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00384] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 93 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 123. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00385] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 93 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 124. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00386] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 94 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 125. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00387] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 95 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 126. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00388] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 127. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00389] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 124. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00390] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 125. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00391] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 96 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 126. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00392] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 97 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 128. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00393] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 98 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 129. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00394] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 99 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 130. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00395] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 100 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 131. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00396] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 101 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 132. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00397] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 102 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 133. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00398] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 103 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 134. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00399] In some embodiments, there is provided a full-length anti-C5aR1 antibody comprising IgG4 constant domains, wherein the anti-C5aR1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 102 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 135. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. Binding affinity [00400] Binding affinity can be indicated by Kd, Koff, Kon, or Ka. The term "Koff", as used herein, is intended to refer to the off-rate constant for dissociation of an antibody from the antibody /antigen complex, as determined from a kinetic selection set up. The term "Kon", as used herein, is intended to refer to the on-rate constant for association of an antibody to the antigen to form the antibody/antigen complex. The term dissociation constant "Kd", as used herein, refers to the dissociation constant of a particular antibody- antigen interaction, and describes the concentration of antigen required to occupy one half of all of the antibody-binding domains present in a solution of antibody molecules at equilibrium, and is equal to Koff/Kon. The measurement of Kd presupposes that all binding agents are in solution. In the case where the antibody is tethered to a cell wall, e.g., in a yeast expression system, the corresponding equilibrium rate constant is expressed as EC50, which gives a good approximation of Kd. The affinity constant, Ka, is the inverse of the dissociation constant, Kd. [00401] The dissociation constant (Kd) is used as an indicator showing affinity of antibody moieties to antigens. For example, easy analysis is possible by the Scatchard method using antibodies marked with a variety of marker agents, as well as by using Biacore (made by Amersham Biosciences), analysis of biomolecular interactions by surface plasmon resonance, according to the user's manual and attached kit. The Kd value that can be derived using these methods is expressed in units of M. An antibody that specifically binds to a target may have a Kd of, for example, ≤ 10-7 M, ≤ 10-8 M, ≤ 10-9 M, ≤ 10-10 M, ≤ 10-11 M, ≤ 10-12 M, or ≤ 10-13 M. [00402] Binding specificity of the antibody can be determined experimentally by methods known in the art. Such methods comprise, but are not limited to, Western blots, ELISA-, RIA-, ECL-, IRMA-, EIA-, BIAcore-tests and peptide scans. [00403] In some embodiments, the anti-C5aR1 antibody specifically binds to a target C5aR1 with a Kd of about 10-7 M to about 10-13 M (such as about 10-7 M to about 10-13 M, about 10-8 M to about 10-13 M, about 10-9 M to about 10-13 M, or about 10-10 M to about 10-12 M). Thus in some embodiments, the Kd of the binding between the anti-C5aR1 antibody and C5aR1, is about 10-7 M to about 10-13 M, about 1×10-7 M to about 5×10-13 M, about 10-7 M to about 10-12 M, about 10-7 M to about 10-11 M, about 10-7 M to about 10-10 M, about 10-7 M to about 10-9 M, about 10-8 M to about 10-13 M, about 1×10-8 M to about 5×10-13 M, about 10- 8 M to about 10-12 M, about 10-8 M to about 10-11 M, about 10-8 M to about 10-10 M, about 10- 8 M to about 10-9 M, about 5×10-9 M to about 1×10-13 M, about 5×10-9 M to about 1×10-12 M, about 5×10-9 M to about 1×10-11 M, about 5×10-9 M to about 1×10-10 M, about 10-9 M to about 10-13 M, about 10-9 M to about 10-12 M, about 10-9 M to about 10-11 M, about 10-9 M to about 10-10 M, about 5×10-10 M to about 1×10-13 M, about 5×10-10 M to about 1×10-12 M, about 5×10-10 M to about 1×10-11 M, about 10-10 M to about10-13 M, about 1×10-10 M to about 5×10-13 M, about 1×10-10 M to about 1×10-12 M, about 1×10-10 M to about 5×10-12 M, about 1×10-10 M to about 1×10-11 M, about 10-11 M to about 10-13 M, about 1×10-11 M to about 5×10-13 M, about 10-11 M to about 10-12 M, or about 10-12 M to about 10-13 M. In some embodiments, the Kd of the binding between the anti-C5aR1 antibody and a C5aR1 is about 10-7 M to about 10-13 M. [00404] In some embodiments, the Kd of the binding between the anti-C5aR1 antibody and a non-target is more than the Kd of the binding between the anti-C5aR1 antibody and the target, and is herein referred to in some embodiments as the binding affinity, of the anti- C5aR1 antibody to the target (e.g., C5aR1) is higher than that to a non-target. In some embodiments, the non-target is an antigen that is not C5aR1. In some embodiments, the Kd of the binding between the anti-C5aR1 antibody (against C5aR1) and a non-C5aR1 target can be at least about 10 times, such as about 10-100 times, about 100-1000 times, about 103-104 times, about 104-105 times, about 105-106 times, about 106-107 times, about 107-108 times, about 108-109 times, about 109-1010 times, about 1010-1011 times, or about 1011-1012 times of the Kd of the binding between the anti-C5aR1 antibody and a target C5aR1. [00405] In some embodiments, the anti-C5aR1 antibody binds to a non-target with a Kd of about 10-1 M to about 10-6 M (such as about 10-1 M to about 10-6 M, about 10-1 M to about 10-5 M, or about 10-2 M to about 10-4 M). In some embodiments, the non-target is an antigen that is not C5aR1. Thus in some embodiments, the Kd of the binding between the anti-C5aR1 antibody and a non-C5aR1 target is about 10-1 M to about 10-6 M, about 1×10-1 M to about 5×10-6 M, about 10-1 M to about 10-5 M, about 1×10-1 M to about 5×10-5 M, about 10-1 M to about 10-4 M, about 1×10-1 M to about 5×10-4 M, about 10-1 M to about 10-3 M, about 1×10-1 M to about 5×10-3 M, about 10-1 M to about 10-2 M, about 10-2 M to about 10-6 M, about 1×10-2 M to about 5×10-6 M, about 10-2 M to about 10-5 M, about 1×10-2 M to about 5×10-5 M, about 10-2 M to about 10-4 M, about 1×10-2 M to about 5×10-4 M, about 10-2 M to about 10-3 M, about 10-3 M to about 10-6 M, about 1×10-3 M to about 5×10-6 M, about 10-3 M to about 10-5 M, about 1×10-3 M to about 5×10-5 M, about 10-3 M to about 10-4 M, about 10-4 M to about 10-6 M, about 1×10-4 M to about 5×10-6 M, about 10-4 M to about 10-5 M, or about 10-5 M to about 10-6 M. [00406] In some embodiments, when referring to that the anti-C5aR1 antibody specifically recognizes a target C5aR1 at a high binding affinity, and binds to a non-target at a low binding affinity, the anti-C5aR1 antibody will bind to the target C5aR1 with a Kd of about 10-7 M to about 10-13 M (such as about 10-7 M to about 10-13 M, about 10-8 M to about 10-13 M, about 10-9 M to about 10-13 M, or about 10-10 M to about 10-12 M), and will bind to the non-target with a Kd of about 10-1 M to about 10-6 M (such as about 10-1 M to about 10-6 M, about 10-1 M to about 10-5 M, or about 10-3 M to about 10-4 M). [00407] In some embodiments, when referring to that the anti-C5aR1 antibody specifically recognizes C5aR1, the binding affinity of the anti-C5aR1 antibody is compared to that of a control anti-C5aR1 antibody (such as avdoralimab). In some embodiments, the Kd of the binding between the control anti-C5aR1 antibody and C5aR1 can be at least about 2 times, such as about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, about 9 times, about 10 times, about 10-100 times, about 100-1000 times, about 103-104 times of the Kd of the binding between the anti-C5aR1 antibody described herein and C5aR1. Nucleic Acids [00408] Nucleic acid molecules encoding the anti-C5aR1 antibodies are also contemplated. In some embodiments, there is provided a nucleic acid (or a set of nucleic acids) encoding a full-length anti-C5aR1 antibody, including any of the full-length anti- C5aR1 antibodies described herein. In some embodiments, the nucleic acid (or a set of nucleic acids) encoding the anti-C5aR1 antibody described herein may further comprises a nucleic acid sequence encoding a peptide tag (such as protein purification tag, e.g., His-tag, HA tag). [00409] Also contemplated here are isolated host cells comprising an anti-C5aR1 antibody, an isolated nucleic acid encoding the polypeptide components of the anti-C5aR1 antibody, or a vector comprising a nucleic acid encoding the polypeptide components of the anti-C5aR1 antibody described herein. [00410] The present application also includes variants to these nucleic acid sequences. For example, the variants include nucleotide sequences that hybridize to the nucleic acid sequences encoding the anti-C5aR1 antibodies of the present application under at least moderately stringent hybridization conditions. [00411] The present application also provides vectors in which a nucleic acid of the present application is inserted. [00412] In brief summary, the expression of an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) by a natural or synthetic nucleic acid encoding the anti-C5aR1 antibody can be achieved by inserting the nucleic acid into an appropriate expression vector, such that the nucleic acid is operably linked to 5' and 3' regulatory elements, including for example a promoter (e.g., a lymphocyte-specific promoter) and a 3' untranslated region (UTR). The vectors can be suitable for replication and integration in eukaryotic host cells. Typical cloning and expression vectors contain transcription and translation terminators, initiation sequences, and promoters useful for regulation of the expression of the desired nucleic acid sequences. [00413] The nucleic acids of the present application may also be used for nucleic acid immunization and gene therapy, using standard gene delivery protocols. Methods for gene delivery are known in the art. See, e.g., U.S. Pat. Nos.5,399,346, 5,580,859, 5,589,466, incorporated by reference herein in their entireties. In some embodiments, the application provides a gene therapy vector. [00414] The nucleic acid can be cloned into a number of types of vectors. For example, the nucleic acid can be cloned into a vector including, but not limited to a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors, and sequencing vectors. [00415] Further, the expression vector may be provided to a cell in the form of a viral vector. Viral vector technology is well known in the art and is described, for example, in Green and Sambrook (2013, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York), and in other virology and molecular biology manuals. Viruses which are useful as vectors include, but are not limited to, retroviruses, adenoviruses, adeno- associated viruses, herpes viruses, and lentiviruses. In general, a suitable vector contains an origin of replication functional in at least one organism, a promoter sequence, convenient restriction endonuclease sites, and one or more selectable markers (see, e.g., WO 01/96584; WO 01/29058; and U.S. Pat. No. 6,326,193).
[00416] A number of viral based systems have been developed for gene transfer into mammalian cells. For example, retroviruses provide a convenient platform for gene delivery systems. A selected gene can be inserted into a vector and packaged in retroviral particles using techniques known in the art. The recombinant virus can then be isolated and delivered to cells of the subject either in vivo or ex vivo. A number of retroviral systems are known in the art In some embodiments, adenovirus vectors are used. A number of adenovirus vectors are known in the art. In some embodiments, lentivirus vectors are used. Vectors derived from retroviruses such as the lentivirus are suitable tools to achieve long-term gene transfer since they allow long-term, stable integration of a transgene and its propagation in daughter cells. Lentiviral vectors have the added advantage over vectors derived from onco-retroviruses such as murine leukemia viruses in that they can transduce non-proliferating cells, such as hepatocytes. They also have the added advantage of low immunogenicity.
[00417] Additional promoter elements, e.g., enhancers, regulate the frequency of transcriptional initiation. Typically, these are located in the region 30-110 bp upstream of the start site, although a number of promoters have recently been shown to contain functional elements downstream of the start site as well. The spacing between promoter elements frequently is flexible, so that promoter function is preserved when elements are inverted or moved relative to one another. In the thymidine kinase (tk) promoter, the spacing between promoter elements can be increased to 50 bp apart before activity begins to decline.
[00418] One example of a suitable promoter is the immediate early cytomegalovirus (CMV) promoter sequence. This promoter sequence is a strong constitutive promoter sequence capable of driving high levels of expression of any polynucleotide sequence operatively linked thereto. Another example of a suitable promoter is Elongation Factor-1α (EF-1α). However, other constitutive promoter sequences may also be used, including, but not limited to the simian virus 40 (SV40) early promoter, mouse mammary tumor virus (MMTV), human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus promoter, as well as human gene promoters such as, but not limited to, the actin promoter, the myosin promoter, the hemoglobin promoter, and the creatine kinase promoter. Further, the application should not be limited to the use of constitutive promoters. Inducible promoters are also contemplated as part of the application. The use of an inducible promoter provides a molecular switch capable of turning on expression of the polynucleotide sequence to which it is operatively linked when such expression is desired, or turning off the expression when expression is not desired. Examples of inducible promoters include, but are not limited to a metallothionine promoter, a glucocorticoid promoter, a progesterone promoter, and a tetracycline promoter. [00419] In some embodiments, the expression of the anti-C5aR1 antibody is inducible. In some embodiments, a nucleic acid sequence encoding the anti-C5aR1 antibody is operably linked to an inducible promoter, including any inducible promoter described herein. Inducible promoters [00420] The use of an inducible promoter provides a molecular switch capable of turning on expression of the polynucleotide sequence to which it is operatively linked when such expression is desired, or turning off the expression when expression is not desired. Exemplary inducible promoter systems for use in eukaryotic cells include, but are not limited to, hormone-regulated elements (e.g., see Mader, S. and White, J. H. (1993) Proc. Natl. Acad. Sci. USA 90:5603-5607), synthetic ligand-regulated elements (see, e.g., Spencer, D. M. et al. (1993) Science 262: 1019-1024) and ionizing radiation-regulated elements (e.g., see Manome, Y. et al. (1993) Biochemistry 32: 10607-10613; Datta, R. et al. (1992) Proc. Natl. Acad. Sci. USA 89: 1014- 10153). Further exemplary inducible promoter systems for use in in vitro or in vivo mammalian systems are reviewed in Gingrich et al. (1998) Annual Rev. Neurosci 21:377-405. In some embodiments, the inducible promoter system for use to express the anti-C5aR1 antibody is the Tet system. In some embodiments, the inducible promoter system for use to express the anti-C5aR1 antibody is the lac repressor system from E. coli. [00421] An exemplary inducible promoter system for use in the present application is the Tet system. Such systems are based on the Tet system described by Gossen et al. (1993). In an exemplary embodiment, a polynucleotide of interest is under the control of a promoter that comprises one or more Tet operator (TetO) sites. In the inactive state, Tet repressor (TetR) will bind to the TetO sites and repress transcription from the promoter. In the active state, e.g., in the presence of an inducing agent such as tetracycline (Tc), anhydrotetracycline, doxycycline (Dox), or an active analog thereof, the inducing agent causes release of TetR from TetO, thereby allowing transcription to take place. Doxycycline is a member of the tetracycline family of antibiotics having the chemical name of 1-dimethylamino-2,4a,5,7,12- pentahydroxy-11-methyl-4,6-dioxo-1,4a,11,11a,12,12a-hexahydrotetracene-3-carboxamide. [00422] In one embodiment, a TetR is codon-optimized for expression in mammalian cells, e.g., murine or human cells. Most amino acids are encoded by more than one codon due to the degeneracy of the genetic code, allowing for substantial variations in the nucleotide sequence of a given nucleic acid without any alteration in the amino acid sequence encoded by the nucleic acid. However, many organisms display differences in codon usage, also known as "codon bias" (i.e., bias for use of a particular codon(s) for a given amino acid). Codon bias often correlates with the presence of a predominant species of tRNA for a particular codon, which in turn increases efficiency of mRNA translation. Accordingly, a coding sequence derived from a particular organism (e.g., a prokaryote) may be tailored for improved expression in a different organism (e.g., a eukaryote) through codon optimization. [00423] Other specific variations of the Tet system include the following "Tet-Off" and "Tet-On" systems. In the Tet-Off system, transcription is inactive in the presence of Tc or Dox. In that system, a tetracycline-controlled transactivator protein (tTA), which is composed of TetR fused to the strong transactivating domain of VP16 from Herpes simplex virus, regulates expression of a target nucleic acid that is under transcriptional control of a tetracycline-responsive promoter element (TRE). The TRE is made up of TetO sequence concatamers fused to a promoter (commonly the minimal promoter sequence derived from the human cytomegalovirus (hCMV) immediate-early promoter). In the absence of Tc or Dox, tTA binds to the TRE and activates transcription of the target gene. In the presence of Tc or Dox, tTA cannot bind to the TRE, and expression from the target gene remains inactive. [00424] Conversely, in the Tet-On system, transcription is active in the presence of Tc or Dox. The Tet-On system is based on a reverse tetracycline-controlled transactivator, rtTA. Like tTA, rtTA is a fusion protein comprised of the TetR repressor and the VP16 transactivation domain. However, a four amino acid change in the TetR DNA binding moiety alters rtTA's binding characteristics such that it can only recognize the tetO sequences in the TRE of the target transgene in the presence of Dox. Thus, in the Tet-On system, transcription of the TRE-regulated target gene is stimulated by rtTA only in the presence of Dox. [00425] Another inducible promoter system is the lac repressor system from E. coli (See Brown et al., Cell 49:603-612 (1987)). The lac repressor system functions by regulating transcription of a polynucleotide of interest operably linked to a promoter comprising the lac operator (lacO). The lac repressor (lacR) binds to LacO, thus preventing transcription of the polynucleotide of interest. Expression of the polynucleotide of interest is induced by a suitable inducing agent, e.g., isopropyl-β-D-thiogalactopyranoside (IPTG). [00426] In order to assess the expression of a polypeptide or portions thereof, the expression vector to be introduced into a cell can also contain either a selectable marker gene or a reporter gene or both to facilitate identification and selection of expressing cells from the population of cells sought to be transfected or infected through viral vectors. In other aspects, the selectable marker may be carried on a separate piece of DNA and used in a co- transfection procedure. Both selectable markers and reporter genes may be flanked with appropriate regulatory sequences to enable expression in the host cells. Useful selectable markers include, for example, antibiotic-resistance genes, such as neo and the like. [00427] Reporter genes are used for identifying potentially transfected cells and for evaluating the functionality of regulatory sequences. In general, a reporter gene is a gene that is not present in or expressed by the recipient organism or tissue and that encodes a polypeptide whose expression is manifested by some easily detectable property, e.g., enzymatic activity. Expression of the reporter gene is assayed at a suitable time after the DNA has been introduced into the recipient cells. Suitable reporter genes may include genes encoding luciferase, β-galactosidase, chloramphenicol acetyl transferase, secreted alkaline phosphatase, or the green fluorescent protein gene (e.g., Ui-Tel et al., 2000 FEBS Letters 479: 79-82). Suitable expression systems are well known and may be prepared using known techniques or obtained commercially. In general, the construct with the minimal 5' flanking region showing the highest level of expression of reporter gene is identified as the promoter. Such promoter regions may be linked to a reporter gene and used to evaluate agents for the ability to modulate promoter-driven transcription. [00428] In some embodiments, there is provided nucleic acid encoding a full-length anti-C5aR1 antibody according to any of the full-length anti-C5aR1 antibodies described herein. In some embodiments, the nucleic acid comprises one or more nucleic acid sequences encoding the heavy and light chains of the full-length anti-C5aR1 antibody. In some embodiments, each of the one or more nucleic acid sequences are contained in separate vectors. In some embodiments, at least some of the nucleic acid sequences are contained in the same vector. In some embodiments, all of the nucleic acid sequences are contained in the same vector. Vectors may be selected, for example, from the group consisting of mammalian expression vectors and viral vectors (such as those derived from retroviruses, adenoviruses, adeno-associated viruses, herpes viruses, and lentiviruses). [00429] Methods of introducing and expressing genes into a cell are known in the art. In the context of an expression vector, the vector can be readily introduced into a host cell, e.g., mammalian, bacterial, yeast, or insect cell by any method in the art. For example, the expression vector can be transferred into a host cell by physical, chemical, or biological means. [00430] Physical methods for introducing a polynucleotide into a host cell include calcium phosphate precipitation, lipofection, particle bombardment, microinjection, electroporation, and the like. Methods for producing cells comprising vectors and/or exogenous nucleic acids are well-known in the art. See, for example, Green and Sambrook (2013, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York). In some embodiments, the introduction of a polynucleotide into a host cell is carried out by calcium phosphate transfection. [00431] Biological methods for introducing a polynucleotide of interest into a host cell include the use of DNA and RNA vectors. Viral vectors, and especially retroviral vectors, have become the most widely used method of inserting genes into mammalian, e.g., human cells. Other viral vectors can be derived from lentivirus, poxviruses, herpes simplex virus 1, adenoviruses and adeno-associated viruses, and the like. See, for example, U.S. Pat. Nos. 5,350,674 and 5,585,362. [00432] Chemical means for introducing a polynucleotide into a host cell include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. An exemplary colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (e.g., an artificial membrane vesicle). [00433] In the case where a non-viral delivery system is utilized, an exemplary delivery vehicle is a liposome. The use of lipid formulations is contemplated for the introduction of the nucleic acids into a host cell (in vitro, ex vivo or in vivo). In another aspect, the nucleic acid may be associated with a lipid. The nucleic acid associated with a lipid may be encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the oligonucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. Lipid, lipid/DNA or lipid/expression vector associated compositions are not limited to any particular structure in solution. For example, they may be present in a bilayer structure, as micelles, or with a "collapsed" structure. They may also simply be interspersed in a solution, possibly forming aggregates that are not uniform in size or shape. Lipids are fatty substances which may be naturally occurring or synthetic lipids. For example, lipids include the fatty droplets that naturally occur in the cytoplasm as well as the class of compounds which contain long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, amino alcohols, and aldehydes. [00434] Regardless of the method used to introduce exogenous nucleic acids into a host cell or otherwise expose a cell to the inhibitor of the present application, in order to confirm the presence of the recombinant DNA sequence in the host cell, a variety of assays may be performed. Such assays include, for example, "molecular biological" assays well known to those of skill in the art, such as Southern and Northern blotting, RT-PCR and PCR; "biochemical" assays, such as detecting the presence or absence of a particular peptide, e.g., by immunological means (ELISAs and Western blots) or by assays described herein to identify agents falling within the scope of the application. Preparation of anti-C5aR1 antibodies [00435] In some embodiments, the anti-C5aR1 antibody is a monoclonal antibody or derived from a monoclonal antibody. In some embodiments, the anti-C5aR1 antibody comprises VH and VL domains, or variants thereof, from the monoclonal antibody. In some embodiments, the anti-C5aR1 antibody further comprises CH1 and CL domains, or variants thereof, from the monoclonal antibody. Monoclonal antibodies can be prepared, e.g., using known methods in the art, including hybridoma methods, phage display methods, or using recombinant DNA methods. Additionally, exemplary phage display methods are described herein and in the Examples below. [00436] In a hybridoma method, a hamster, mouse, or other appropriate host animal is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes can be immunized in vitro. The immunizing agent can include a polypeptide or a fusion protein of the protein of interest. Generally, peripheral blood lymphocytes ("PBLs") are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell. Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine, and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells can be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT medium"), which prevents the growth of HGPRT-deficient cells. [00437] In some embodiments, the immortalized cell lines fuse efficiently, support stable high-level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. In some embodiments, the immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, California and the American Type Culture Collection, Manassas, Virginia. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies. [00438] The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the polypeptide. The binding specificity of monoclonal antibodies produced by the hybridoma cells can be determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., 107:220 (1980). [00439] After the desired hybridoma cells are identified, the clones can be sub-cloned by limiting dilution procedures and grown by standard methods. Goding, supra. Suitable culture media for this purpose include, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal. [00440] The monoclonal antibodies secreted by the sub-clones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography. [00441] In some embodiments, according to any of the anti-C5aR1 antibodies described herein, the anti-C5aR1 antibody comprises sequences from a clone selected from an antibody library (such as a phage library presenting scFv or Fab fragments). The clone may be identified by screening combinatorial libraries for antibody fragments with the desired activity or activities. For example, a variety of methods are known in the art for generating phage display libraries and screening such libraries for antibodies possessing the desired binding characteristics. Such methods are reviewed, e.g., in Hoogenboom et al., Methods in Molecular Biology 178:1-37 (O'Brien et al., ed., Human Press, Totowa, N.J., 2001) and further described, e.g., in McCafferty et al., Nature 348:552-554; Clackson et al., Nature 352: 624-628 (1991); Marks et al., J. Mol. Biol.222: 581-597 (1992); Marks and Bradbury, Methods in Molecular Biology 248:161-175 (Lo, ed., Human Press, Totowa, N.J., 2003); Sidhu et al., J. Mol. Biol.338(2): 299-310 (2004); Lee et al., J. Mol. Biol.340(5): 1073-1093 (2004); Fellouse, Proc. Natl. Acad. Sci. USA 101(34): 12467-12472 (2004); and Lee et al., J. Immunol. Methods 284(1-2): 119-132(2004). [00442] In certain phage display methods, repertoires of VH and VL genes are separately cloned by polymerase chain reaction (PCR) and recombined randomly in phage libraries, which can then be screened for antigen-binding phage as described in Winter et al., Ann. Rev. Immunol., 12: 433-455 (1994). Phage typically display antibody fragments, either as scFv fragments or as Fab fragments. Libraries from immunized sources provide high- affinity antibodies to the immunogen without the requirement of constructing hybridomas. Alternatively, the naive repertoire can be cloned (e.g., from human) to provide a single source of antibodies to a wide range of non-self and also self-antigens without any immunization as described by Griffiths et al., EMBO J, 12: 725-734 (1993). Finally, naive libraries can also be made synthetically by cloning unrearranged V-gene segments from stem cells, and using PCR primers containing random sequence to encode the highly variable CDR3 regions and to accomplish rearrangement in vitro, as described by Hoogenboom and Winter, J. Mol. Biol., 227: 381-388 (1992). Patent publications describing human antibody phage libraries include, for example: U.S. Pat. No.5,750,373, and US Patent Publication Nos.2005/0079574, 2005/0119455, 2005/0266000, 2007/0117126, 2007/0160598, 2007/0237764, 2007/0292936, and 2009/0002360. [00443] The anti-C5aR1 antibodies can be prepared using phage display to screen libraries for anti-C5aR1 antibody moieties specific to the target C5aR1. The library can be a human scFv phage display library having a diversity of at least 1 × 109 (such as at least about any of 1 × 109, 2.5 × 109, 5 × 109, 7.5 × 109, 1 × 1010, 2.5 × 1010, 5 × 1010, 7.5 × 1010, or 1 × 1011) unique human antibody fragments. In some embodiments, the library is a naïve human library constructed from DNA extracted from human PMBCs and spleens from healthy donors, encompassing all human heavy and light chain subfamilies. In some embodiments, the library is a naïve human library constructed from DNA extracted from PBMCs isolated from patients with various diseases, such as patients with autoimmune diseases, cancer patients, and patients with infectious diseases. In some embodiments, the library is a semi- synthetic human library, wherein heavy chain CDR3 is completely randomized, with all amino acids (with the exception of cysteine) equally likely to be present at any given position (see, e.g., Hoet, R.M. et al., Nat. Biotechnol.23(3):344-348, 2005). In some embodiments, the heavy chain CDR3 of the semi-synthetic human library has a length from about 5 to about 24 (such as about any of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24) amino acids. In some embodiments, the library is a fully-synthetic phage display library. In some embodiments, the library is a non-human phage display library. [00444] Phage clones that bind to the target C5aR1 with high affinity can be selected by iterative binding of phage to the target C5aR1, which is bound to a solid support (such as, for example, beads for solution panning or mammalian cells for cell panning), followed by removal of non-bound phage and by elution of specifically bound phage. The bound phage clones are then eluted and used to infect an appropriate host cell, such as E. coli XL1-Blue, for expression and purification. The panning can be performed for multiple (such as about any of 2, 3, 4, 5, 6 or more) rounds with solution panning, cell panning, or a combination of both, to enrich for phage clones binding specifically to the target C5aR1. Enriched phage clones can be tested for specific binding to the target C5aR1 by any methods known in the art, including for example ELISA and FACS. [00445] An alternative method for screening antibody libraries is to display the protein on the surface of yeast cells. Wittrup et al. (US Patent Nos.6,699,658 and 6,696,251) have developed a method for a yeast cell display library. In this yeast display system, a component involves the yeast agglutinin protein (Aga1), which is anchored to the yeast cell wall. Another component involves a second subunit of the agglutinin protein Aga2, which can display on the surface yeast cells through disulfide bonds to Aga1 protein. The protein Aga1 is expressed from a yeast chromosome after the Aga1 gene integration. A library of single chain variable fragments (scFv) is fused genetically to Aga2 sequence in the yeast display plasmid, which, after transformation, is maintained in yeast episomally with a nutritional marker. Both of the Aga1 and Aga2 proteins were expressed under the control of the galactose-inducible promoter. [00446] Human antibody V gene repertoire (VH and VK fragments) are obtained by PCR method using a pool of degenerate primers (Sblattero, D. & Bradbury, A. Immunotechnology 3, 271-2781998). The PCR templates are from the commercially available RNAs or cDNAs, including PBMC, spleen, lymph nodes, bone marrow and tonsils. Separate VH and VK PCR libraries were combined, then assembled together in the scFv format by overlap extension PCR ( Sheets, M.D. et al., Proc. Natl. Acad. Sci. USA 95, 6157- 6162 1998.). To construct the yeast scFv display library, the resultant scFv PCR products are cloned into the yeast display plasmid in the yeasts by homologous recombination. (Chao, G, et al., Nat Protoc.2006;1(2):755-68. Miller KD, et al., Current Protocols in Cytometry 4.7.1- 4.7.30, 2008). [00447] The anti-C5aR1 antibodies can be discovered using mammalian cell display systems in which antibody moieties are displayed on the cell surface and those specific to the target C5aR1 are isolated by the antigen-guided screening method, as described in U.S. patent No.7,732,195B2. A Chinese hamster ovary (CHO) cell library representing a large set of human IgG antibody genes can be established and used to discover the clones expressing high-affinity antibody genes. Another display system has been developed to enable simultaneous high-level cell surface display and secretion of the same protein through alternate splicing, where the displayed protein phenotype remains linked to genotype, allowing soluble secreted antibody to be simultaneously characterized in biophysical and cell-based functional assays. This approach overcomes many limitations of previous mammalian cell display, enabling direct selection and maturation of antibodies in the form of full-length, glycosylated IgGs (Peter M. Bowers, et al., Methods 2014,65:44-56). Transient expression systems are suitable for a single round of antigen selection before recovery of the antibody genes and therefore most useful for the selection of antibodies from smaller libraries. Stable episomal vectors offer an attractive alternative. Episomal vectors can be transfected at high efficiency and stably maintained at low copy number, permitting multiple rounds of panning and the resolution of more complex antibody libraries. [00448] The IgG library is based on germline sequence V-gene segments joined to rearranged (D)J regions isolated from a panel of human donors. RNA collected from 2000 human blood samples was reverse-transcribed into cDNA, and the VH and VK fragments were amplified using VH- and VK-specific primers and purified by gel extraction. IgG libraries were generated by sub-cloning the VH and VK fragments into the display vectors containing IgG1 or K constant regions respectively and then electroporating into or transducing 293T cells. To generate the scFv antibody display library, scFvs were generated by linking VH and VK, and then sub-cloned into the display vector, which were then electroporated into or transduce 293T cells. As we known, the IgG library is based on germline sequence V-gene segments joined to rearranged (D)J regions isolated from a panel of donors, the donor can be a mouse, rat, rabbit, or monkey. [00449] Monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Patent No.4,816,567. DNA encoding the monoclonal antibodies of the application can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). Hybridoma cells as described above or C5aR1- specific phage clones of the application can serve as a source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also can be modified, for example, by substituting the coding sequence for human heavy- and light-chain constant domains and/or framework regions in place of the homologous non-human sequences (U.S. Patent No.4,816,567; Morrison et al., supra) or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Such a non- immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the application, or can be substituted for the variable domains of one antigen-combining site of an antibody of the application to create a chimeric bivalent antibody. [00450] The antibodies can be monovalent antibodies. Methods for preparing monovalent antibodies are known in the art. For example, one method involves recombinant expression of immunoglobulin light chain and modified heavy chain. The heavy chain is truncated generally at any point in the Fc region so as to prevent heavy-chain crosslinking. Alternatively, the relevant cysteine residues are substituted with another amino acid residue or are deleted so as to prevent crosslinking. [00451] In vitro methods are also suitable for preparing monovalent antibodies. Digestion of antibodies to produce fragments thereof, particularly Fab fragments, can be accomplished using any method known in the art. [00452] Antibody variable domains with the desired binding specificities (antibody- antigen combining sites) can be fused to immunoglobulin constant-domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. In some embodiments, the first heavy-chain constant region (CH1) containing the site necessary for light-chain binding is present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. Human and Humanized Antibodies [00453] The anti-C5aR1 antibodies (e.g., full-length anti-C5aR1 antibodies) can be humanized antibodies or human antibodies. Humanized forms of non-human (e.g., murine) antibody moieties are chimeric immunoglobulins, immunoglobulin chains, or fragments thereof (such as Fv, Fab, Fab', F(ab')2, scFv, or other antigen-binding subsequences of antibodies) that typically contain minimal sequence derived from non-human immunoglobulin. Humanized antibody moieties include human immunoglobulins, immunoglobulin chains, or fragments thereof (recipient antibody) in which residues from a CDR of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat, or rabbit having the desired specificity, affinity, and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibody moieties can also comprise residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody can comprise substantially at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin, and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. [00454] Generally, a humanized antibody has one or more amino acid residues introduced into it from a source that is non-human. These non-human amino acid residues are often referred to as "import" residues, which are typically taken from an "import" variable domain. According to some embodiments, humanization can be essentially performed following the method of Winter and co-workers (Jones et al., Nature, 321: 522-525 (1986); Riechmann et al., Nature, 332: 323-327 (1988); Verhoeyen et al., Science, 239: 1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such "humanized" antibody moieties are antibody moieties (U.S. Patent No.4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In practice, humanized antibody moieties are typically human antibody moieties in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies. [00455] As an alternative to humanization, human antibody moieties can be generated. For example, it is now possible to produce transgenic animals (e.g., mice) that are capable, upon immunization, of producing a full repertoire of human antibodies in the absence of endogenous immunoglobulin production. For example, it has been described that the homozygous deletion of the antibody heavy-chain joining region (JH) gene in chimeric and germ-line mutant mice results in complete inhibition of endogenous antibody production. Transfer of the human germ-line immunoglobulin gene array into such germ-line mutant mice will result in the production of human antibodies upon antigen challenge. See, e.g., Jakobovits et al., PNAS USA, 90:2551 (1993); Jakobovits et al., Nature, 362:255-258 (1993); Bruggemann et al., Year in Immunol., 7:33 (1993); U.S. Patent Nos.5,545,806, 5,569,825, 5,591,669; 5,545,807; and WO 97/17852. Alternatively, human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed that closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Patent Nos.5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; and 5,661,016, and Marks et al., Bio/Technology, 10: 779-783 (1992); Lonberg et al., Nature, 368: 856-859 (1994); Morrison, Nature, 368: 812-813 (1994); Fishwild et al., Nature Biotechnology, 14: 845-851 (1996); Neuberger, Nature Biotechnology, 14: 826 (1996); Lonberg and Huszar, Intern. Rev. Immunol., 13: 65-93 (1995). [00456] Human antibodies may also be generated by in vitro activated B cells (see U.S. Patents 5,567,610 and 5,229,275) or by using various techniques known in the art, including phage display libraries. Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991). The techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies. Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p.77 (1985) and Boerner et al., J. Immunol., 147(1): 86-95 (1991). Anti-C5aR1 antibody variants [00457] In some embodiments, amino acid sequences of the anti-C5aR1 antibody variants (e.g., full-length anti-C5aR1 antibody) provided herein are contemplated. For example, it may be desirable to improve the binding affinity and/or other biological properties of the antibody. Amino acid sequences of an antibody variant may be prepared by introducing appropriate modifications into the nucleotide sequence encoding the antibody, or by peptide synthesis. Such modifications include, for example, deletions from, and/or insertions into and/or substitutions of residues within the amino acid sequences of the antibody. Any combination of deletion, insertion, and substitution can be made to arrive at the final construct, provided that the final construct possesses the desired characteristics, e.g., antigen-binding. [00458] In some embodiments, anti-C5aR1 antibody variants having one or more amino acid substitutions are provided. Sites of interest for substitutional mutagenesis include the HVRs and FRs. Amino acid substitutions may be introduced into an antibody of interest and the products screened for a desired activity, e.g., improved bioactivity, retained/improved antigen binding, decreased immunogenicity, or improved ADCC or CDC. [00459] Conservative substitutions are shown in Table 4 below. TABLE 4: CONSERVATIVE SUBSTITUTIONS
Figure imgf000157_0001
[00460] Amino acids may be grouped into different classes according to common side- chain properties: a. hydrophobic: Norleucine, Met, Ala, Val, Leu, Ile; b. neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; c. acidic: Asp, Glu; d. basic: His, Lys, Arg; e. residues that influence chain orientation: Gly, Pro; f. aromatic: Trp, Tyr, Phe. [00461] Non-conservative substitutions will entail exchanging a member of one of these classes for another class. [00462] An exemplary substitutional variant is an affinity matured antibody, which may be conveniently generated, e.g., using phage display-based affinity maturation techniques. Briefly, one or more CDR residues are mutated and the variant antibody moieties displayed on phage and screened for a particular biological activity (e.g., bioactivity based on neutrophil C5a-induced CD11b upregulation inhibition assay or binding affinity). Alterations (e.g., substitutions) may be made in HVRs, e.g., to improve bioactivity based on neutrophil C5a-induced CD11b upregulation inhibition assay or binding affinity. Such alterations may be made in HVR "hotspots", e.g., residues encoded by codons that undergo mutation at high frequency during the somatic maturation process (see, e.g., Chowdhury, Methods Mol. Biol. 207:179-196 (2008)), and/or specificity determining residues (SDRs), with the resulting variant VH and VL being tested for binding affinity. Affinity maturation by constructing and reselecting from secondary libraries has been described, e.g., in Hoogenboom et al., in Methods in Molecular Biology 178:1-37 (O'Brien et al., ed., Human Press, Totowa, NJ, (2001)). [00463] In some embodiments of affinity maturation, diversity is introduced into the variable genes chosen for maturation by any of a variety of methods (e.g., error-prone PCR, chain shuffling, or oligonucleotide-directed mutagenesis). A secondary library is then created. The library is then screened to identify any antibody variants with the desired affinity. Another method to introduce diversity involves HVR-directed approaches, in which several HVR residues (e.g., 4-6 residues at a time) are randomized. HVR residues involved in antigen binding may be specifically identified, e.g., using alanine scanning mutagenesis or modeling. CDR-H3 and CDR-L3 in particular are often targeted. [00464] In some embodiments, substitutions, insertions, or deletions may occur within one or more HVRs so long as such alterations do not substantially reduce the ability of the antibody to bind antigen. For example, conservative alterations (e.g., conservative substitutions as provided herein) that do not substantially reduce binding affinity may be made in HVRs. Such alterations may be outside of HVR "hotspots" or SDRs. In some embodiments of the variant VH and VL sequences provided above, each HVR either is unaltered, or contains no more than one, two or three amino acid substitutions. [00465] A useful method for identification of residues or regions of an antibody that may be targeted for mutagenesis is called "alanine scanning mutagenesis" as described by Cunningham and Wells (1989) Science, 244:1081-1085. In this method, a residue or group of target residues (e.g., charged residues such as Arg, Asp, His, Lys, and Glu) are identified and replaced by a neutral or negatively charged amino acid (e.g., Ala or Glu) to determine whether the interaction of the antibody with antigen is affected. Further substitutions may be introduced at the amino acid locations to demonstrate functional sensitivity to the initial substitutions. Alternatively, or additionally, a crystal structure of an antigen-antibody complex can be determined to identify contact points between the antibody and antigen. Such contact residues and neighboring residues may be targeted or eliminated as candidates for substitution. Variants may be screened to determine whether they contain the desired properties. [00466] Amino acid sequence insertions include amino- and/or carboxyl-terminal fusions ranging in length from one residue to polypeptides containing a hundred or more residues, as well as intrasequence insertions of single or multiple amino acid residues. Examples of terminal insertions include an antibody with an N-terminal methionyl residue. Other insertional variants of the antibody molecule include the fusion to the N- or C-terminus of the antibody to an enzyme (e.g., for ADEPT) or a polypeptide which increases the serum half-life of the antibody. Fc Region Variants [00467] In some embodiments, one or more amino acid modifications may be introduced into the Fc region of an antibody (e.g., a full-length anti-C5aR1 antibody or anti- C5aR1 Fc fusion protein) provided herein, thereby generating an Fc region variant. In some embodiments, the Fc region variant has enhanced ADCC effector function, often related to binding to Fc receptors (FcRs). In some embodiments, the Fc region variant has decreased ADCC effector function. There are many examples of changes or mutations to Fc sequences that can alter effector function. For example, WO 00/42072 and Shields et al., J Biol. Chem. 9(2): 6591-6604 (2001) describe antibody variants with improved or diminished binding to FcRs. The contents of those publications are specifically incorporated herein by reference. [00468] Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) is a mechanism of action of therapeutic antibodies against tumor cells. ADCC is a cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell (e.g., a cancer cell), whose membrane-surface antigens have been bound by specific antibodies (e.g., an anti-C5aR1 antibody). The typical ADCC involves activation of NK cells by antibodies. An NK cell expresses CD16 which is an Fc receptor. This receptor recognizes, and binds to, the Fc portion of an antibody bound to the surface of a target cell. The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII. Binding of the Fc receptor to the Fc region of an antibody results in NK cell activation, release of cytolytic granules and consequent target cell apoptosis. The contribution of ADCC to tumor cell killing can be measured with a specific test that uses NK-92 cells that have been transfected with a high- affinity FcR. Results are compared to wild-type NK-92 cells that do not express the FcR. [00469] In some embodiments, the application contemplates an anti-C5aR1 antibody variant (such as a full-length anti-C5aR1 antibody variant) comprising an Fc region that possesses some but not all effector functions, which makes it a desirable candidate for applications in which the half-life of the anti-C5aR1 antibody in vivo is important yet certain effector functions (such as CDC and ADCC) are unnecessary or deleterious. In vitro and/or in vivo cytotoxicity assays can be conducted to confirm the reduction/depletion of CDC and/or ADCC activities. For example, Fc receptor (FcR) binding assays can be conducted to ensure that the antibody lacks FcγR binding (hence likely lacking ADCC activity), but retains FcRn binding ability. The primary cells for mediating ADCC, NK cells, express FcγRIII only, whereas monocytes express FcγRI, FcγRII and FcγRIII. FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol. 9:457-492 (1991). Non-limiting examples of in vitro assays to assess ADCC activity of a molecule of interest is described in U.S. Pat. No.5,500,362 (see, e.g., Hellstrom, I. et al., Proc. Nat'l Acad. Sci. USA 83:7059-7063 (1986)) and Hellstrom, I. et al., Proc. Nat'l Acad. Sci. USA 82:1499-1502 (1985); U.S. Pat. No.5,821,337 (see Bruggemann, M. et al., J. Exp. Med.166:1351-1361 (1987)). Alternatively, non-radioactive assay methods may be employed (see, for example, ACTI™ non-radioactive cytotoxicity assay for flow cytometry (CellTechnology, Inc. Mountain View, Calif.; and CYTOTOX 96™ non-radioactive cytotoxicity assay (Promega, Madison, Wis.). Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and Natural Killer (NK) cells. Alternatively, or additionally, ADCC activity of the molecule of interest may be assessed in vivo, e.g., in an animal model such as that disclosed in Clynes et al., Proc. Nat'l Acad. Sci. USA 95:652-656 (1998). C1q binding assays may also be carried out to confirm that the antibody is unable to bind C1q and hence lacks CDC activity. See, e.g., C1q and C3c binding ELISA in WO 2006/029879 and WO 2005/100402. To assess complement activation, a CDC assay may be performed (see, for example, Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996); Cragg, M. S. et al., Blood 101:1045-1052 (2003); and Cragg, M. S. and M. J. Glennie, Blood 103:2738-2743 (2004)). FcRn binding and in vivo clearance/half-life determinations can also be performed using methods known in the art (see, e.g., Petkova, S. B. et al., Int'l. Immunol. 18(12):1759-1769 (2006)). [00470] Antibodies with reduced effector function include those with substitution of one or more of Fc region residues 238, 265, 269, 270, 297, 327 and 329 (U.S. Pat. No. 6,737,056). Such Fc mutants include Fc mutants with substitutions at two or more of amino acid positions 265, 269, 270, 297 and 327, including the so-called "DANA" Fc mutant with substitution of residues 265 and 297 to alanine (U.S. Pat. No.7,332,581). [00471] Certain antibody variants with improved or diminished binding to FcRs are described. (See, e.g., U.S. Pat. No.6,737,056; WO 2004/056312, and Shields et al., J. Biol. Chem.9(2): 6591-6604 (2001).) [00472] In some embodiments, there is provided an anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) variant comprising a variant Fc region comprising one or more amino acid substitutions which improve ADCC. In some embodiments, the variant Fc region comprises one or more amino acid substitutions which improve ADCC, wherein the substitutions are at positions 298, 333, and/or 334 of the variant Fc region (EU numbering of residues). In some embodiments, the anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) variant comprises the following amino acid substitution in its variant Fc region: S298A, E333A, and K334A. [00473] In some embodiments, alterations are made in the Fc region that result in altered (i.e., either improved or diminished) C1q binding and/or Complement Dependent Cytotoxicity (CDC), e.g., as described in U.S. Pat. No.6,194,551, WO 99/51642, and Idusogie et al., J. Immunol.164: 4178-4184 (2000). [00474] In some embodiments, there is provided an anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) variant comprising a variant Fc region comprising one or more amino acid substitutions which increase half-life and/or improve binding to the neonatal Fc receptor (FcRn). Antibodies with increased half-lives and improved binding to FcRn are described in US2005/0014934A1 (Hinton et al.). Those antibodies comprise an Fc region with one or more substitutions therein which improve binding of the Fc region to FcRn. Such Fc variants include those with substitutions at one or more of Fc region residues: 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or 434, e.g., substitution of Fc region residue 434 (U.S. Pat. No.7,371,826). [00475] See also Duncan & Winter, Nature 322:738-40 (1988); U.S. Pat. No. 5,648,260; U.S. Pat. No.5,624,821; and WO 94/29351 concerning other examples of Fc region variants. [00476] Anti-C5aR1 antibodies (such as full-length anti-C5aR1 antibodies) comprising any of the Fc variants described herein, or combinations thereof, are contemplated. Glycosylation Variants [00477] In some embodiments, an anti-C5aR1 antibody (such as a full-length anti- C5aR1 antibody) provided herein is altered to increase or decrease the extent to which the anti-C5aR1 antibody is glycosylated. Addition or deletion of glycosylation sites to an anti- C5aR1 antibody may be conveniently accomplished by altering the amino acid sequence of the anti-C5aR1 antibody or polypeptide portion thereof such that one or more glycosylation sites are created or removed. [00478] Wherein the anti-C5aR1 antibody comprises an Fc region, the carbohydrate attached thereto may be altered. Native antibodies produced by mammalian cells typically comprise a branched, biantennary oligosaccharide that is generally attached by an N-linkage to Asn297 of the CH2 domain of the Fc region. See, e.g., Wright et al., TIBTECH 15:26-32 (1997). The oligosaccharide may include various carbohydrates, e.g., mannose, N-acetyl glucosamine (GlcNAc), galactose, and sialic acid, as well as a fucose attached to a GlcNAc in the "stem" of the biantennary oligosaccharide structure. In some embodiments, modifications of the oligosaccharide in an anti-C5aR1 antibody of the application may be made in order to create anti-C5aR1 antibody variants with certain improved properties. [00479] The N-glycans attached to the CH2 domain of Fc is heterogeneous. Antibodies or Fc fusion proteins generated in CHO cells are fucosylated by fucosyltransferase activity. See Shoji-Hosaka et al., J. Biochem.2006, 140:777- 83. Normally, a small percentage of naturally occurring afucosylated IgGs may be detected in human serum. N-glycosylation of the Fc is important for binding to FcγR; and afucosylation of the N-glycan increases Fc's binding capacity to FcγRIIIa. Increased FcγRIIIa binding can enhance ADCC, which can be advantageous in certain antibody therapeutic applications in which cytotoxicity is desirable. [00480] In some embodiments, an enhanced effector function can be detrimental when Fc-mediated cytotoxicity is undesirable. In some embodiments, the Fc fragment or CH2 domain is not glycosylated. In some embodiments, the N-glycosylation site in the CH2 domain is mutated to prevent from glycosylation. [00481] In some embodiments, anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) variants are provided comprising an Fc region wherein a carbohydrate structure attached to the Fc region has reduced fucose or lacks fucose, which may improve ADCC function. Specifically, anti-C5aR1 antibodies are contemplated herein that have reduced fucose relative to the amount of fucose on the same anti-C5aR1 antibody produced in a wild- type CHO cell. That is, they are characterized by having a lower amount of fucose than they would otherwise have if produced by native CHO cells (e.g., a CHO cell that produce a native glycosylation pattern, such as, a CHO cell containing a native FUT8 gene). In some embodiments, the anti-C5aR1 antibody is one wherein less than about 50%, 40%, 30%, 20%, 10%, or 5% of the N-linked glycans thereon comprise fucose. For example, the amount of fucose in such an anti-C5aR1 antibody may be from 1% to 80%, from 1% to 65%, from 5% to 65% or from 20% to 40%. In some embodiments, the anti-C5aR1 antibody is one wherein none of the N-linked glycans thereon comprise fucose, i.e., wherein the anti-C5aR1 antibody is completely without fucose, or has no fucose or is afucosylated. The amount of fucose is determined by calculating the average amount of fucose within the sugar chain at Asn297, relative to the sum of all glycostructures attached to Asn 297 (e.g., complex, hybrid and high mannose structures) as measured by MALDI-TOF mass spectrometry, as described in WO 2008/077546, for example. Asn297 refers to the asparagine residue located at about position 297 in the Fc region (EU numbering of Fc region residues); however, Asn297 may also be located about ±3 amino acids upstream or downstream of position 297, i.e., between positions 294 and 300, due to minor sequence variations in antibodies. Such fucosylation variants may have improved ADCC function. See, e.g., US Patent Publication Nos. US 2003/0157108 (Presta, L.); US 2004/0093621 (Kyowa Hakko Kogyo Co., Ltd). Examples of publications related to "defucosylated" or "fucose-deficient" antibody variants include: US 2003/0157108; WO 2000/61739; WO 2001/29246; US 2003/0115614; US 2002/0164328; US 2004/0093621; US 2004/0132140; US 2004/0110704; US 2004/0110282; US 2004/0109865; WO 2003/085119; WO 2003/084570; WO 2005/035586; WO 2005/035778; WO2005/053742; WO2002/031140; Okazaki et al., J. Mol. Biol.336:1239-1249 (2004); Yamane-Ohnuki et al., Biotech. Bioeng.87: 614 (2004). Examples of cell lines capable of producing defucosylated antibodies include Lec13 CHO cells deficient in protein fucosylation (Ripka et al., Arch. Biochem. Biophys.249:533-545 (1986); US Pat Appl No US 2003/0157108 A1, Presta, L; and WO 2004/056312 A1, Adams et al., especially at Example 11), and knockout cell lines, such asα-1,6-fucosyltransferase gene, FUT8, knockout CHO cells (see, e.g., Yamane-Ohnuki et al., Biotech. Bioeng.87: 614 (2004); Kanda, Y. et al., Biotechnol. Bioeng.94(4):680-688 (2006); and WO2003/085107). [00482] Anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) variants are further provided with bisected oligosaccharides, e.g., in which a biantennary oligosaccharide attached to the Fc region of the anti-C5aR1 antibody is bisected by GlcNAc. Such anti- C5aR1 antibody (such as a full-length anti-C5aR1 antibody) variants may have reduced fucosylation and/or improved ADCC function. Examples of such antibody variants are described, e.g., in WO 2003/011878 (Jean-Mairet et al.); U.S. Pat. No.6,602,684 (Umana et al.); US 2005/0123546 (Umana et al.), and Ferrara et al., Biotechnology and Bioengineering, 93(5): 851-861 (2006). Anti-C5aR1 antibody (such as full-length anti-C5aR1 antibody) variants with at least one galactose residue in the oligosaccharide attached to the Fc region are also provided. Such anti-C5aR1 antibody variants may have improved CDC function. Such antibody variants are described, e.g., in WO 1997/30087 (Patel et al.); WO 1998/58964 (Raju, S.); and WO 1999/22764 (Raju, S.). [00483] In some embodiments, the anti-C5aR1 antibody (such as a full-length anti- C5aR1 antibody) variants comprising an Fc region are capable of binding to an FcγRIII. In some embodiments, the anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) variants comprising an Fc region have ADCC activity in the presence of human effector cells (e.g., T cell) or have increased ADCC activity in the presence of human effector cells compared to the otherwise same anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) comprising a human wild-type IgG1Fc region. Cysteine Engineered Variants [00484] In some embodiments, it may be desirable to create cysteine engineered anti- C5aR1 antibodies (such as a full-length anti-C5aR1 antibody) in which one or more amino acid residues are substituted with cysteine residues. In some embodiments, the substituted residues occur at accessible sites of the anti-C5aR1 antibody. By substituting those residues with cysteine, reactive thiol groups are thereby positioned at accessible sites of the anti- C5aR1 antibody and may be used to conjugate the anti-C5aR1 antibody to other moieties, such as drug moieties or linker-drug moieties, to create an anti-C5aR1 immunoconjugate, as described further herein. Cysteine engineered anti-C5aR1 antibodies (e.g., full-length anti- C5aR1 antibodies) may be generated as described, e.g., in U.S. Pat. No.7,521,541. Derivatives [00485] In some embodiments, an anti-C5aR1 antibody (such as a full-length anti- C5aR1 antibody) provided herein may be further modified to contain additional non- proteinaceous moieties that are known in the art and readily available. The moieties suitable for derivatization of the anti-C5aR1 antibody include but are not limited to water soluble polymers. Non-limiting examples of water soluble polymers include, but are not limited to, polyethylene glycol (PEG), copolymers of ethylene glycol/propylene glycol, carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone, poly-1,3- dioxolane, poly-1,3,6-trioxane, ethylene/maleic anhydride copolymer, polyaminoacids (either homopolymers or random copolymers), and dextran or poly(n-vinyl pyrrolidone)polyethylene glycol, propropylene glycol homopolymers, prolypropylene oxide/ethylene oxide co- polymers, polyoxyethylated polyols (e.g., glycerol), polyvinyl alcohol, and mixtures thereof. Polyethylene glycol propionaldehyde may have advantages in manufacturing due to its stability in water. The polymer may be of any molecular weight, and may be branched or unbranched. The number of polymers attached to the anti-C5aR1 antibody may vary, and if more than one polymer are attached, they can be the same or different molecules. In general, the number and/or type of polymers used for derivatization can be determined based on considerations including, but not limited to, the particular properties or functions of anti- C5aR1 antibody to be improved, whether the anti-C5aR1 antibody derivative will be used in a therapy under defined conditions, etc. Pharmaceutical Compositions [00486] Also provided herein are compositions (such as pharmaceutical compositions, also referred to herein as formulations) comprising any of the anti-C5aR1 antibodies (such as a full-length anti-C5aR1 antibody), nucleic acids encoding the antibodies, vectors comprising the nucleic acids encoding the antibodies, or host cells comprising the nucleic acids or vectors described herein. In some embodiments, there is provided a pharmaceutical composition comprising any one of the anti-C5aR1 antibodies described herein and a pharmaceutically acceptable carrier. [00487] Suitable formulations of the anti-C5aR1 antibodies are obtained by mixing an anti-C5aR1 antibody having the desired degree of purity with optional pharmaceutically acceptable carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions. Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propylparaben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as olyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g., Zn-protein complexes); and/or non-ionic surfactants such as TWEEN™, PLURONICS™ or polyethylene glycol (PEG). Exemplary formulations are described in WO98/56418, expressly incorporated herein by reference. Lyophilized formulations adapted for subcutaneous administration are described in WO97/04801. Such lyophilized formulations may be reconstituted with a suitable diluent to a high protein concentration and the reconstituted formulation may be administered subcutaneously to the individual to be treated herein. Lipofectins or liposomes can be used to deliver the anti-C5aR1 antibodies of this application into cells. [00488] The formulation herein may also contain one or more active compounds in addition to the anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. For example, it may be desirable to further provide an anti-neoplastic agent, a growth inhibitory agent, a cytotoxic agent, or a chemotherapeutic agent in addition to the anti-C5aR1 antibody. Such molecules are suitably present in combination in amounts that are effective for the purpose intended. The effective amount of such other agents depends on the amount of anti-C5aR1 antibody present in the formulation, the type of disease or disorder or treatment, and other factors discussed above. These are generally used in the same dosages and with administration routes as described herein or about from 1 to 99% of the heretofore employed dosages. [00489] The anti-C5aR1 antibodies (e.g., full-length anti-C5aR1 antibodies) may also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules) or in macroemulsions. Sustained-release preparations may be prepared. [00490] Sustained-release preparations of the anti-C5aR1 antibodies (e.g., full-length anti-C5aR1 antibodies) can be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody (or fragment thereof), which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate ), or poly(vinylalcohol)), polylactides (U.S. Pat. No.3,773,919), copolymers of L-glutamic acid and ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D (-)-3-hydroxybutyric acid. While polymers such as ethylene- vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydro gels release proteins for shorter time periods. When encapsulated antibody remain in the body for a long time, they can denature or aggregate as a result of exposure to moisture at 37°C, resulting in a loss of biological activity and possible changes in immunogenicity. Rational strategies can be devised for stabilization of anti-C5aR1 antibodies depending on the mechanism involved. For example, if the aggregation mechanism is discovered to be intermolecular S-S bond formation through thio-disulfide interchange, stabilization can be achieved by modifying sulfhydryl residues, lyophilizing from acidic solutions, controlling moisture content, using appropriate additives, and developing specific polymer matrix compositions. [00491] In some embodiments, the anti-C5aR1 antibody (such as a full-length anti- C5aR1 antibody) is formulated in a buffer comprising a citrate, NaCl, acetate, succinate, glycine, polysorbate 80 (Tween 80), or any combination of the foregoing. [00492] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by, e.g., filtration through sterile filtration membranes. Methods of treatment using anti-C5aR1 antibodies [00493] The anti-C5aR1 antibodies (e.g., full-length anti-C5aR1 antibodies) and/or compositions of the application can be administered to individuals (e.g., mammals such as humans) to treat a disease and/or disorder associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers). These diseases include, but are not limited to allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. The present application thus in some embodiments provides a method of treating a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) in an individual comprising administering to the individual an effective amount of a composition (such as a pharmaceutical composition) comprising an anti-C5aR1 antibody (e.g., a full-length anti-C5aR1 antibody), such as any one of the anti- C5aR1 antibodies (e.g., full-length anti-C5aR1 antibodies) described herein. In some embodiments, the individual is human. [00494] For example, in some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) specifically binding to an epitope on human C5aR1 , wherein the epitope comprises amino acid residues of human C5aR1. In some embodiments, the anti-C5aR1 antibody is a full-length antibody. In some embodiments, the full-length anti- C5aR1 antibody is an IgG1 or IgG4 antibody. In some embodiments, the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human. [00495] For example, in some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising SYWMN (SEQ ID NO: 1); an HC-CDR2 comprising RIDPX1X2X3X4TRYNQKFED (SEQ ID NO: 72), wherein X1 is G, R, S, or Y, X2 is D, R, or S, X3 is G or S, and X4 is E or G; and an HC- CDR3 comprising FVX1PX2GX3FX4Y (SEQ ID NO: 73), wherein X1 is I or W, X2 is L, M, Q, S, or V, X3 is A or G, and X4 is A or Q; and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSX1X2X3X4HSNGX5TYLH (SEQ ID NO: 74), wherein X1 is Q or R, X2 is Q or S, X3 is L or P, X4 is L or V, and X5 is N or Q; an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising X1QSTX2VPPT (SEQ ID NO: 75), wherein X1 is M or S, and X2 is F, H, L, R, V, or Y. In some embodiments, the anti-C5aR1 antibody is a full-length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody. In some embodiments, the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human. [00496] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-15, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-31, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-44, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-64, or a variant thereof comprising up to 5 amino acid substitutions in the LC- CDRs. [00497] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a VH comprising the amino acid sequence of any one of SEQ ID NOs: 76-91 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 76-91, and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 104-120, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 104- 120. [00498] In some embodiments, the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00499] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00500] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 76 and a VL comprising the amino acid sequence of SEQ ID NO: 104. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00501] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 77 and a VL comprising the amino acid sequence of SEQ ID NO: 105. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00502] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00503] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 78 and a VL comprising the amino acid sequence of SEQ ID NO: 106. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00504] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00505] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 79 and a VL comprising the amino acid sequence of SEQ ID NO: 107. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00506] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00507] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 80 and a VL comprising the amino acid sequence of SEQ ID NO: 106. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00508] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00509] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 81 and a VL comprising the amino acid sequence of SEQ ID NO: 108. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00510] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00511] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 82 and a VL comprising the amino acid sequence of SEQ ID NO: 109. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00512] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00513] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 83 and a VL comprising the amino acid sequence of SEQ ID NO: 110. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00514] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00515] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 83 and a VL comprising the amino acid sequence of SEQ ID NO: 111. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00516] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00517] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 84 and a VL comprising the amino acid sequence of SEQ ID NO: 112. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00518] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00519] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 85 and a VL comprising the amino acid sequence of SEQ ID NO: 113. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00520] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00521] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 86 and a VL comprising the amino acid sequence of SEQ ID NO: 107. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00522] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00523] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 87 and a VL comprising the amino acid sequence of SEQ ID NO: 114. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00524] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00525] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 88 and a VL comprising the amino acid sequence of SEQ ID NO: 115. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00526] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 89 and a VL comprising the amino acid sequence of SEQ ID NO: 116. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00527] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 90 and a VL comprising the amino acid sequence of SEQ ID NO: 117. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00528] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 91 and a VL comprising the amino acid sequence of SEQ ID NO: 118. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00529] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 89 and a VL comprising the amino acid sequence of SEQ ID NO: 119. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00530] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 89 and a VL comprising the amino acid sequence of SEQ ID NO: 120. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00531] For example, in some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising SGYSWH (SEQ ID NO: 2); an HC-CDR2 comprising YIHSSGDTDYNPSLKR (SEQ ID NO: 16); and an HC-CDR3 comprising SIGDY (SEQ ID NO: 32); and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 45); an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising SQSTHVPWT (SEQ ID NO: 65). In some embodiments, the anti-C5aR1 antibody is a full-length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody. In some embodiments, the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human. [00532] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00533] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a VH comprising the amino acid sequence of any one of SEQ ID NOs: 92-96 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 92-96, and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 121-127, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 121- 127. [00534] In some embodiments, the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00535] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising: a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. [00536] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 92 and a VL comprising the amino acid sequence of SEQ ID NO: 121. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00537] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 93 and a VL comprising the amino acid sequence of SEQ ID NO: 122. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00538] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 93 and a VL comprising the amino acid sequence of SEQ ID NO: 123. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00539] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 93 and a VL comprising the amino acid sequence of SEQ ID NO: 124. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00540] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 94 and a VL comprising the amino acid sequence of SEQ ID NO: 125. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00541] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 95 and a VL comprising the amino acid sequence of SEQ ID NO: 126. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00542] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 96 and a VL comprising the amino acid sequence of SEQ ID NO: 127. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00543] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 96 and a VL comprising the amino acid sequence of SEQ ID NO: 124. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00544] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 96 and a VL comprising the amino acid sequence of SEQ ID NO: 125. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00545] In some embodiments, the anti-C5aR1 antibody provided herein comprises a VH comprising the amino acid sequence of SEQ ID NO: 96 and a VL comprising the amino acid sequence of SEQ ID NO: 126. In some embodiments, the anti-C5aR1 antibody provided herein is a full-length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00546] For example, in some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. In some embodiments, the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody. In some embodiments, the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human. [00547] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a VH comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 97, and a VL comprising the amino acid sequence of SEQ ID NO: 128, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 128. [00548] In some embodiments, the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00549] For example, in some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. In some embodiments, the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody. In some embodiments, the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human. [00550] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a VH comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 98, and a VL comprising the amino acid sequence of SEQ ID NO: 129, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 129. [00551] In some embodiments, the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00552] For example, in some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. In some embodiments, the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody. In some embodiments, the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human. [00553] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a VH comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 99, and a VL comprising the amino acid sequence of SEQ ID NO: 130, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 130. [00554] In some embodiments, the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00555] For example, in some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. In some embodiments, the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody. In some embodiments, the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human. [00556] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a VH comprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 100, and a VL comprising the amino acid sequence of SEQ ID NO: 131, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 131. [00557] In some embodiments, the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00558] For example, in some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 48, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. In some embodiments, the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody. In some embodiments, the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human. [00559] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a VH comprising the amino acid sequence of SEQ ID NO: 101 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 101, and a VL comprising the amino acid sequence of SEQ ID NO: 132, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 132. [00560] In some embodiments, the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00561] For example, in some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. In some embodiments, the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody. In some embodiments, the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human. [00562] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a VH comprising the amino acid sequence of SEQ ID NO: 102 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 102, and a VL comprising the amino acid sequence of SEQ ID NO: 133, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 133. [00563] In some embodiments, the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00564] For example, in some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 50, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs.In some embodiments, the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody. In some embodiments, the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human. [00565] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a VH comprising the amino acid sequence of SEQ ID NO: 103 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 103, and a VL comprising the amino acid sequence of SEQ ID NO: 134, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 134. [00566] In some embodiments, the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00567] For example, in some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full-length anti-C5aR1 antibody) comprising a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC- CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71, or a variant thereof comprising up to 5 amino acid substitutions in the LC-CDRs. In some embodiments, the anti-C5aR1 antibody is a full- length antibody. In some embodiments, the full-length anti-C5aR1 antibody is an IgG1 or IgG4 antibody. In some embodiments, the disease or condition is selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. In some embodiments, the individual is human. [00568] In some embodiments, there is provided a method of treating an individual having a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ) comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-C5aR1 antibody (e.g., full- length anti-C5aR1 antibody) comprising a VH comprising the amino acid sequence of SEQ ID NO: 102 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 102, and a VL comprising the amino acid sequence of SEQ ID NO: 135, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 135. [00569] In some embodiments, the anti-C5aR1 antibody provided herein is a full- length anti-C5aR1 antibody comprising IgG1 or IgG4 constant domains. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 136. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 137. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 138. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 139. [00570] In some embodiments, the individual is a mammal (e.g., human, non-human primate, rat, mouse, cow, horse, pig, sheep, goat, dog, cat, etc.). In some embodiments, the individual is a human. In some embodiments, the individual is a clinical patient, a clinical trial volunteer, an experimental animal, etc. In some embodiments, the individual is younger than about 60 years old (including for example younger than about any of 50, 40, 30, 25, 20, 15, or 10 years old). In some embodiments, the individual is older than about 60 years old (including for example older than about any of 70, 80, 90, or 100 years old). In some embodiments, the individual is diagnosed with or genetically prone to one or more of the diseases or disorders described herein (such as inflammatory diseases, autoimmune disease, or cancers ). In some embodiments, the individual has one or more risk factors associated with one or more diseases or disorders described herein. [00571] The present application in some embodiments provides a method of delivering an anti-C5aR1 antibody (such as any one of the anti-C5aR1 antibodies described herein, e.g., an isolated anti-C5aR1 antibody) to a cell producing C5aR1 in an individual, the method comprising administering to the individual a composition comprising the anti-C5aR1 antibody. [00572] Many diagnostic methods for inflammatory diseases, autoimmune disease, or cancers or any other disease associated with C5aR1 signaling and the clinical delineation of those diseases are known in the art. Such methods include, but are not limited to, e.g., immunohistochemistry, PCR, and fluorescent in situ hybridization (FISH). [00573] In some embodiments, the anti-C5aR1 antibodies (e.g., full-length anti-C5aR1 antibodies) and/or compositions of the application are administered in combination with a second, third, or fourth agent (including, e.g., radiation therapy, chemotherapy, therapy for autoimmune disease or other drug therapy (e.g., corticosteroid therapy)) to treat diseases or disorders associated with C5aR1 signaling. [00574] Cancer treatments can be evaluated by, e.g., tumor regression, tumor weight or size shrinkage, time to progression, duration of survival, progression free survival, overall response rate, duration of response, quality of life, protein expression and/or activity. Approaches to determining efficacy of the therapy can be employed, including for example, measurement of response through radiological imaging. [00575] In some embodiments, the efficacy of treatment is measured as the percentage tumor growth inhibition (% TGI), calculated using the equation 100-(T/C × 100), where T is the mean relative tumor volume of the treated tumor, and C is the mean relative tumor volume of a non-treated tumor. In some embodiments, the %TGI is about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, or more than 95%. In some embodiments, the efficacy of treatment is measured using shape change of granulocytes and/or increase in the survival of granulocytes. In some embodiments, the efficacy of treatment is measured by the increase of cytokine secretion by monocytes. [00576] In some embodiments, the efficiency of treatment is measured as the percentage human neutrophils migration inhibition. In some embodiments, the antibody inhibits migration to less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% compared to the level of migration observed in the presence of 10nM C5a and no anti- C5aR antibody. [00577] In some embodiments, the efficiency of treatment can be evaluated by, e.g., the inhibition of C5a induced neutrophil maturation based on secondary effects such as CD11b and CD62L expression. CD11b and CD62L are maturation markers of neutrophils as they are up and down-regulated, respectively, upon activation by C5a/C5aR interaction. In some embodiments, the IC50 as determined in an CD11b upregulation assay is below 3.5μg/ml, such as 3.0μg/ml, such as 2.5μg/ml, such as 2.0μg/ml, or such as 1.5μg/ml or even below such as 1.0μg/ml. Dosing and method of administering the anti-C5aR1 antibodies [00578] The dose of the anti-C5aR1 antibody (such as isolated anti-C5aR1 antibody) compositions administered to an individual (such as a human) may vary with the particular composition, the mode of administration, and the type of disease being treated. In some embodiments, the amount of the composition (such as composition comprising isolated anti- C5aR1 antibody) is effective to result in an objective response (such as a partial response or a complete response) in the treatment of inflammatory diseases, autoimmune disease, or cancers. In some embodiments, the amount of the anti-C5aR1 antibody composition is sufficient to result in a complete response in the individual. In some embodiments, the amount of the anti-C5aR1 antibody composition is sufficient to result in a partial response in the individual. In some embodiments, the amount of the anti-C5aR1 antibody composition administered (for example when administered alone) is sufficient to produce an overall response rate of more than about any of 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 64%, 65%, 70%, 75%, 80%, 85%, or 90% among a population of individuals treated with the anti-C5aR1 antibody composition. Responses of an individual to the treatment of the methods described herein can be determined, for example, based on RECIST level or human neutrophils migration inhibition level. [00579] In some embodiments, the amount of the composition (such as composition comprising isolated anti-C5aR1 antibody) is sufficient to control symptoms and reduce the risk of exacerbations of the individual. In some embodiments, the amount of the composition is sufficient to control symptoms and reduce the risk of exacerbations of the individual. In some embodiments, the amount of the composition (for example when administered along) is sufficient to produce clinical benefit of more than about any of 50%, 60%, 70%, or 77% among a population of individuals treated with the anti-C5aR1 antibody composition. [00580] In some embodiments, the amount of the composition (such as composition comprising isolated anti-C5aR1 antibody), alone or in combination with a second, third, and/or fourth agent, is an amount sufficient to control symptoms and reduce the risk of exacerbations in the same subject prior to treatment or compared to the corresponding activity in other subjects not receiving the treatment. Standard methods can be used to measure the magnitude of this effect, such as in vitro assays with purified enzyme, cell-based assays, animal models, or human testing. [00581] In some embodiments, the amount of the anti-C5aR1 antibody (such as a full- length anti-C5aR1 antibody) in the composition is below the level that induces a toxicological effect (i.e., an effect above a clinically acceptable level of toxicity) or is at a level where a potential side effect can be controlled or tolerated when the composition is administered to the individual. [00582] In some embodiments, the amount of the composition is close to a maximum tolerated dose (MTD) of the composition following the same dosing regimen. In some embodiments, the amount of the composition is more than about any of 80%, 90%, 95%, or 98% of the MTD. [00583] In some embodiments, the amount of an anti-C5aR1 antibody (such as a full- length anti-C5aR1 antibody) in the composition is included in a range of about 0.001 μg to about 1000 μg. [00584] In some embodiments of any of the above aspects, the effective amount of anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) in the composition is in the range of about 0.1 μg/kg to about 100 mg/kg of total body weight. [00585] The anti-C5aR1 antibody compositions can be administered to an individual (such as human) via various routes, including, for example, intravenous, intra-arterial, intraperitoneal, intrapulmonary, oral, inhalation, intravesicular, intramuscular, intra-tracheal, subcutaneous, intraocular, intrathecal, transmucosal or transdermal. In some embodiments, sustained continuous release formulation of the composition may be used. In some embodiments, the composition is administered inhaled. In some embodiments, the composition is administered intravenously. In some embodiments, the composition is administered intraportally. In some embodiments, the composition is administered intraarterially. In some embodiments, the composition is administered intraperitoneally. In some embodiments, the composition is administered intrahepatically. In some embodiments, the composition is administered by hepatic arterial infusion. In some embodiments, the administration is to an injection site distal to a first disease site. Articles of Manufacture and Kits [00586] In some embodiments of the application, there is provided an article of manufacture containing materials useful for the treatment of disease or condition associated with C5aR1 signaling, (e.g., inflammatory diseases, autoimmune disease, or cancers) or for delivering an anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) to a cell producing C5aR1 of the individual. The article of manufacture can comprise a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, etc. The containers may be formed from a variety of materials such as glass or plastic. Generally, the container holds a composition which is effective for treating a disease or disorder described herein, and may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). At least one active agent in the composition is an anti-C5aR1 antibody of the application. The label or package insert indicates that the composition is used for treating the particular condition. The label or package insert will further comprise instructions for administering the anti-C5aR1 antibody composition to the patient. Articles of manufacture and kits comprising combinatorial therapies described herein are also contemplated. [00587] Package insert refers to instructions customarily included in commercial packages of therapeutic products that contain information about the indications, usage, dosage, administration, contraindications and/or warnings concerning the use of such therapeutic products. In some embodiments, the package insert indicates that the composition is used for treating disease or condition associated with C5aR1 signaling (such as inflammatory diseases, autoimmune disease, or cancers). In some embodiments, the package insert indicates that the composition is used for treating disease or condition selected from the group consisting of allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies. [00588] Additionally, the article of manufacture may further comprise a second container comprising a pharmaceutically-acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution or dextrose solution. It may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes. [00589] Kits are also provided that are useful for various purposes, e.g., for treatment of disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers), or for delivering an anti-C5aR1 antibody (such as a full- length anti-C5aR1 antibody) to a cell producing C5aR1 of the individual, optionally in combination with the articles of manufacture. Kits of the application include one or more containers comprising anti-C5aR1 antibody composition (or unit dosage form and/or article of manufacture), and in some embodiments, further comprise another agent (such as the agents described herein) and/or instructions for use in accordance with any of the methods described herein. The kit may further comprise a description of selection of individuals suitable for treatment. Instructions supplied in the kits of the application are typically written instructions on a label or package insert (e.g., a paper sheet included in the kit), but machine- readable instructions (e.g., instructions carried on a magnetic or optical storage disk) are also acceptable. [00590] For example, in some embodiments, the kit comprises a composition comprising an anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody). In some embodiments, the kit comprises a) a composition comprising any one of the anti-C5aR1 antibodies described herein, and b) an effective amount of at least one other agent, wherein the other agent enhances the effects (e.g., treatment effect, detecting effect) of the anti-C5aR1 antibody. In some embodiments, the kit comprises a) a composition comprising any one of the anti-C5aR1 antibodies described herein, and b) instructions for administering the anti- C5aR1 antibody composition to an individual for treatment of a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ). In some embodiments, the kit comprises a) a composition comprising any one of the anti-C5aR1 antibodies described herein, b) an effective amount of at least one other agent, wherein the other agent enhances the effect (e.g., treatment effect, detecting effect) of the anti-C5aR1 antibody, and c) instructions for administering the anti-C5aR1 antibody composition and the other agent(s) to an individual for treatment of a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers . The anti-C5aR1 antibody and the other agent(s) can be present in separate containers or in a single container. For example, the kit may comprise one distinct composition or two or more compositions wherein one composition comprises an anti-C5aR1 antibody and another composition comprises another agent. [00591] In some embodiments, the kit comprises a nucleic acid (or a set of nucleic acids) encoding an anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody). In some embodiments, the kit comprises a) a nucleic acid (or a set of nucleic acids) encoding an anti- C5aR1 antibody, and b) a host cell for expressing the nucleic acid (or a set of nucleic acids). In some embodiments, the kit comprises a) a nucleic acid (or a set of nucleic acids) encoding an anti-C5aR1 antibody, and b) instructions for i) expressing the anti-C5aR1 antibody in a host cell, ii) preparing a composition comprising the anti-C5aR1 antibody, and iii) administering the composition comprising the anti-C5aR1 antibody to an individual for the treatment of a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers. In some embodiments, the kit comprises a) a nucleic acid (or a set of nucleic acids) encoding an anti-C5aR1 antibody, b) a host cell for expressing the nucleic acid (or a set of nucleic acids), and c) instructions for i) expressing the anti-C5aR1 antibody in the host cell, ii) preparing a composition comprising the anti-C5aR1 antibody, and iii) administering the composition comprising the anti-C5aR1 antibody to an individual for the treatment of a disease or condition associated with C5aR1 signaling (e.g., inflammatory diseases, autoimmune disease, or cancers ). [00592] The kits of the application are in suitable packaging. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (e.g., sealed Mylar or plastic bags), and the like. Kits may optionally provide additional components such as buffers and interpretative information. The present application thus also provides articles of manufacture, which include vials (such as sealed vials), bottles, jars, flexible packaging, and the like. [00593] The instructions relating to the use of the anti-C5aR1 antibody compositions generally include information as to dosage, dosing schedule, and route of administration for the intended treatment. The containers may be unit doses, bulk packages (e.g., multi-dose packages) or sub-unit doses. For example, kits may be provided that contain sufficient dosages of an anti-C5aR1 antibody (such as a full-length anti-C5aR1 antibody) as disclosed herein to provide effective treatment of an individual for an extended period, such as any of a week, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 7 months, 8 months, 9 months, or more. Kits may also include multiple unit doses of the anti-C5aR1 antibody and pharmaceutical compositions and instructions for use and packaged in quantities sufficient for storage and use in pharmacies, for example, hospital pharmacies and compounding pharmacies. [00594] Those skilled in the art will recognize that several embodiments are possible within the scope and spirit of this application. The application will now be described in greater detail by reference to the following non-limiting examples. The following examples further illustrate the application but, of course, should not be construed as in any way limiting its scope. EXAMPLES [0595] Various features and embodiments of the disclosure are illustrated in the following representative examples, which are intended to be illustrative, and not limiting. Those skilled in the art will readily appreciate that the specific examples are only illustrative of the invention as described more fully in the claims which follow thereafter. Every embodiment and feature described in the application should be understood to be interchangeable and combinable with every embodiment contained within. Example 1: Generation of C5aR1 [0596] This example illustrates the preparation of the various C5aR1 constructs used as antigens in eliciting and screening the anti-C5aR1 antibodies of the present disclosure. [0597] The coding sequence of the human C5aR1 (huC5aR1), musculus C5aR1 (musC5aR1), or cynomolgus monkey C5aR1 (cynoC5aR1) was synthesized and sub-cloned into the expression vector pCDNA3.1 or LV101. The amino acid sequences were provided in Table 5. Table 5 C5aR1 polypeptide sequence
Figure imgf000201_0001
[0598] Proteins were expressed in Expi293 cells and ExpiCHO (Thermo Fisher Scientific) according to the manufacturer’s protocol. Briefly, 293F or CHO cells were transfected with the expression vectors respectively, and the cells were cultured at 37°C, under 8% CO2 and 120rpm for 5 days. Example 2: Generation of Anti-C5aR1 Antibodies Using Hybridoma Methods, Screening and Characterization [0599] This example illustrates the methods of using mouse hybridoma technology to generate anti-C5aR1 antibodies, and methods to screen and select antibodies for further characterization. [0600] Generation of huC5aR1 overexpressing cells [0601] To generate anti-C5aR1 antibodies and examine the binding of these antibodies to huC5aR1 overexpressing cells, Expi293 and ExpiCHO cells stably overexpressing huC5aR1 were used to perform FACS analysis. [0602] The coding sequence of huC5aR1 was cloned into a lentiviral vector (LV101) and the recombinant virus was packaged according to the instruction of the virus packaging kit (Lenti-X™ Packaging Single Shots, Cat# 631275, Takada). The Expi293 cells and ExpiCHO cells were transduced respectively with the recombinant virus and huC5aR1 overexpressing cells were selected by puromycin. [0603] Subtractive Immunization, Viral priming, and Whole Cell overexpressing huC5aR1 Immunizations and fusions: Balb/c and NZB mice were immunized with Expi293 cells. Two days later, mice were treated with cyclophosphamide to delete responding T and B cells. Deletion of responding cells was confirmed by flow cytometry with sera drawn from the mice. Lentiviral constructs coding for huC5aR1 were injected into the mice. One week after viral priming, Expi293 cells overexpressing huC5aR1 were injected into the mice. Endpoint titers were determined by whole cell ELISA as described below. Three days after the last immunization, spleens and lymph nodes were harvested and processed according to standard protocols. Mouse B cells were isolated by EasySep Mouse B cell isolation Kit (StemCell, cat# 19854A) and fused with myeloma cells SP2/0-Ag14 cells (ATCC, CRL 1581) using PEG. Following standard protocols, the fused cells were plated into six-well plates in semi-solid ClonalCell-HY Cloning-Medium D (StemCell, cat# 03804). Monoclonal hybridoma clones were picked into 96 well/plate using Clone Pix 2 Machine (Molecular Devices) and cultured in HT medium. [0604] Whole Cell ELISA assays: After 10-14 days of culture, supernatants were collected and subjected to primary screening by ELISA performed on the surface of intact ExpiCHO cells overexpressing huC5aR1 in 96 well plates (Corning 3365). ExpiCHO cells overexpressing huC5aR1 (50,000/well) were plated in FACS buffer (1× phosphate buffered saline, PBS; 5 mM EDTA; 1% BSA; pH7.4). 50μL of culture supernatant of individual hybridoma clones was added to individual well followed by incubation for 30 min at room temperature (RT; 25ºC). Plates were washed 2 times with FACS buffer, then 50μL/well of goat anti-mouse antibody- AP (Southern Biotech, cat# 1030-04) at 1:2000 dilution was added. The plates were incubated at room temperature for 1 hour, washed 3 times with FACS buffer, resuspended in 1× PBS and developed for 30 minutes by addition of 50μL/well of Sigma Fast p-Nitrophenyl phosphate tablet (pNPP) (Sigma Aldrich, cat#N2770-50SET). Plates were analyzed with Synergy HT (Bio-TEK) at 405 nm. [0605] Purification of hybridoma antibodies: Hybridoma clones were confirmed by primary screen antigen binding whole cell ELISA. Positive clones were scaled up to 30 mL cultures in serum free medium and the antibodies were purified as follows. Supernatant media were clarified by centrifugation at 300g for 10 min to remove cells and by filtration with 0.22-micron filter. Clarified supernatant media was mixed with Protein A resin (Thermo Fisher Scientific, cat# A26458) equilibrated with PBS buffer and incubated with gentle rotation for 1.5 h at room temperature. After incubation, the slurry was loaded into a column and the resin was washed with 10-fold column volumes of PBS buffer containing 0.5M NaCl, then eluted with 0.1M glycine-HCl (pH 2.8). The eluent was quickly neutralized with 1M Tris-HCl (pH 8.5) and the buffer was replaced by PBS. The binding and blocking function of the purified hybridoma antibodies were further validated. [0606] C5a Receptor binding assay of hybridoma hits: The purified hybridoma antibodies were further tested for their ability to bind to huC5aR1, musC5aR1, or cynoC5aR1 by flow cytometry. Expi293 cells overexpressing huC5aR1 (50,000/well) were plated in FACS buffer (1× phosphate buffered saline, PBS; 5 mM EDTA; 1% BSA; pH7.4). 50μL of the individual purified antibodies at the indicated concentration (typically titrations starting at 100nM decreasing in 5-fold increments) was added to individual well followed by incubation for 30 min at room temperature (RT; 25ºC). Plates were washed 2 times with FACS buffer, then 50μL/well of AF488-labeled anti-mouse IgG was added and incubated at RT for 30 min. Cells were washed 2 times with FACS buffer and analyzed by flow cytometry using BD Accuri C6 or Thermofisher Attune NxT. Mean fluorescent values were recorded at each dilution and plotted as the log[Ab] and EC50 values determined in GraphPad Prism 6.0. Parental hybridomas with the desired huC5aR1 and cynoC5aR1 binding were prioritized for subcloning and further characterization. Subcloning was carried out with limited dilution and visual inspection was performed to ensure clonality. Hybridoma subclones were screened with the same binding and blocking assays and selected positive hits were cryopreserved. EC50 values of the hybridoma anti-C5aR1 antibodies for top candidates are shown in Table 6. [0607] As shown in Table 6, the exemplary hybridoma anti-C5aR1 antibodies could bind to huC5aR1. The exemplary hybridoma antibodies 10G1, 6G5 and 1G2 could bind to cynoC5aR1 (data not shown). However, the hybridoma C5aR1 antibodies listed in Table 6 did not bind to musC5aR1 (data not shown). Table 6
Figure imgf000204_0001
[0608] C5aR1-TEV/E-Arrestin-Luc reporter assay: Dual transgenic U2OS cells bearing huC5aR1 coupled to tobacco etch virus (TEV) at the C terminus and E-Arrestin coupled to luciferase with a TEV cleavage site (hereinafter referred to as C5aR1-TEV/E-Arrestin-Luc cells) were used to determine functional inhibition of C5aR1 signal transduction. When C5a is added to these cells, E-Arrestin is recruited to the C5aR1. The C5aR1-coupled TEV enzyme then cleaves the TEV site in the luciferase protein allowing it to fold correctly and resulting in a luciferase signal when substrate is added to the cells. C5aR1-TEV/E-Arrestin- Luc cells ˄BonOpus, Cat#BC050088˅were plated at 10,000 cells/well in 96-well or 3,000 cells/well in 384-well tissue culture-treated plates overnight at 37ºC in McCoy’s media containing 10% FBS. Cells were washed 2 times with serum free McCoy’s, and 50μL of the individual purified hybridoma antibodies at the indicated concentration (typically titrations starting at 100nM decreasing in 3-fold increments) in serum free McCoy’s media was added to individual well followed by incubation for 30 min at RT.50μl of McCoy’s media containing 100nM C5a was added to each well and cells were incubated at 37ºC for 3 hr. Following incubation, the cells were equilibrated at RT for 10 min, then Bright-Glo luciferase substrate (Promega) was added to each well and luminescence was recorded at 5 min increments for 1 hr. Luminescence values were recorded at each dilution and plotted as the log[Ab] and IC50 values were determined in GraphPad Prism 6.0 and summarized in Table 7. [0609] As shown in Table 7, the exemplary hybridoma anti-C5aR1 antibodies exhibited good inhibition activity of C5aR1 function. Table 7
Figure imgf000205_0001
[0610] Neutrophil C5a-induced CD11b upregulation inhibition assay: Primary human whole blood was used to assay CD11b upregulation resulting from C5a stimulation.80μL of whole blood was added to 96-well plates and incubated with 50μL of the individual purified hybridoma antibodies at the indicated concentration (typically titrations starting at 100nM decreasing in 5-fold increments) in Hank’s balanced salt solution (HBSS) at 4ºC for 30 min. C5a was added in 20μL HBSS at 20nM concentrations and the plates were incubated for 25 min at 37ºC. After incubation, the plates were cooled on ice for 5 min and a cocktail containing anti-CD66b, anti-CD14, anti-GR-1, and anti-CD11b were added to each well in 50μL HBSS and incubated for 30 min on ice. Red blood cells (RBC) were then lysed by adding 1.8 ml RBC lysis buffer ˄BD Biosciences, Cat#349202˅to each well for 10 min at RT. Following RBC lysis, plates were washed 2 times with FACS buffer, then fixed with 300μL FACS buffer containing 2% paraformaldehyde. CD11b expression on neutrophils and monocytes was assayed by flow cytometry using ThermoFisher Attune NxT. Mean fluorescent values were recorded at each dilution and plotted as the log[Ab] and IC50 values determined in GraphPad Prism 6.0. IC50 values of the exemplary hybridoma anti-C5aR1 antibodies were summarized in Table 8. [0611] As shown in Table 8, the exemplary hybridoma anti-C5aR1 antibodies exhibited inhibition activity of C5a-induced CD11b upregulation in neutrophil.
Figure imgf000206_0001
[0612] Sequencing and amplification of hybridoma antibody clones [0613] RNA Extraction. Monoclonal anti-huC5aR1 hybridoma hits were grown to a density of 1-3×105 in standard hybridoma medium (DMEM/F12, 10% FBS, 1% Glutamax, 1% pen/strep) for 7-10 days in a T75 flask with >80% cell viability. 1-3 million cells from cultures were pelleted in a 15 mL falcon tube after centrifugation at 300 g for 5 min. Pelleted cells were washed by 5 mL ice cold PBS. PBS was removed and cells were resuspended in 600μL Buffer RLT Plus (Qiagen, cat# 74134). Total RNA was isolated from the lysate following the manufacturing protocol (Qiagen, cat # 74134). [0614] PCR amplification to generate cDNA. The synthesis of cDNA utilizes specific reverse PCR primers in conjunction with switch oligos for heavy and kappa chains. To generate cDNA, one microgram of RNA was used as a template followed by reverse transcription using SMART Scribe Reverse Transcriptase kit from Clontech (TAKARA, cat# 639537). Additionally, the reagents include 10μM primers (Integrated DNA technologies), 10 mM deoxy nucleotide triphosphate mix (New England Biolab, cat# N0447S), H2O, and an 80 U/μL RNAse inhibitor (Invitrogen, cat# 10000840). The constant region-specific reverse primers were used in conjunction with universal forward primer in 5’-RACE PCR reactions. PCR products were gel purified and cloned into TOPO TA vectors (ThermoFisher, cat# 451641) which were then transformed into competent cells (ThermoFisher, cat# 451641). After transformation and blue/white screening, white colonies were picked and grew overnight in LB broth media containing carbenicillin. Miniprep purified plasmids were sequenced using M13 forward and T7-forward primers. The variable domain sequences of anti-huC5aR1 hybridomas are summarized in the Table 2A and Table 3A^ Example 3: In vitro Functional Assays of Anti-C5aR1 chimeric Antibodies [0615] This example illustrates cell-based assays used to characterize the functional activity of the chimeric anti-C5aR1 antibodies. [0616] Generation of recombinant IgG1 versions of anti-C5aR1 antibodies: The recombinant anti-C5aR1 chimeric antibody constructs with heavy and light chain variable domain of mouse anti-C5aR1 antibodies and human constant regions were made by using methods well known in the field. The exemplary human heavy chain constant region and light chain constant region were shown in the Table 3. The expression of recombinant anti-C5aR1 chimeric antibodies was performed using Expi293 expression system in accordance with the instruction provided. The plasmids for the heavy chain and the light chain were co- transfected into the cells at the ratio of 1:1 and the transfected cells were cultured for 6 days before harvest. [0617] Recombinant IgG molecules were purified as the following protocols. Supernatant media were clarified by centrifugation at 300 g for 10 min to remove cells and by filtration with 0.22 μm filter. Clarified supernatant media were mixed with MabSelect Protein A resin equilibrated with PBS buffer and incubated with gentle rotation for 1.5 h at room temperature. After incubation, the slurry was loaded into a column and the resin was washed with 20× column volumes of PBS buffer containing 0.15M NaCl, then eluted with 3× column volumes of 50 mM sodium phosphate (pH 3.0). The pH of the eluent was quickly adjusted to pH 5.2 with 1 M Tris-HCl (pH 9.0) and the buffer was replaced by PBS buffer. [0618] C5a Receptor binding assay: The binding of chimeric anti-C5aR1 antibodies to huC5aR1 overexpressing cells was examined as described above in Example 2. Binding EC50 values for exemplary chimeric antibodies were displayed in Figure 1A. [0619] As shown in Figure 1A, the exemplary chimeric anti-C5aR1 antibodies 10G1 and 1C2 exhibited comparable binding activity to huC5aR1 as compared to their hybridoma antibodies and the chimeric format did not alter their binding function. [0620] C5aR1-TEV/E-Arrestin-Luc reporter assay: Assays using the C5aR1-TEV/E-Arrestin- Luc reporter cells and inhibition of labeled-C5a binding were performed as described above in Example 2. IC50 values for exemplary chimeric anti-C5aR1 antibodies were displayed in Figure 1B. [0621] As shown in Figure 1B, the exemplary chimeric anti-C5aR1 antibodies 10G1 and 1C2 showed comparable inhibition activity of C5aR1 function as compared to their hybridoma antibodies. Example 4: Preparation of Humanized Versions of 10G1 and 1C2 [0622] This example illustrates the preparation of humanized versions of the murine anti- huC5aR1 antibody derived from the hybridoma clone 10G1 and 1C2. [0623] Humanization of anti-huC5aR1 antibody [0624] The light chain variable region (VL) and heavy chain variable region (VH) sequences of murine antibody from hybridoma 10G1 and 1C2 were aligned to human germline antibody sequences respectively. The human germline kappa light chain (Gene ID–V gene: IGKV2_24*01 and IGKV2-30*02) and heavy chain (Gene ID–V gene: IGHV1_69_2*01 and IGHV4-38-2*01) were used as the human frameworks. [0625] The complementarity-determining regions (CDRs) of murine anti-huC5aR1 antibody light chain and heavy chain were grafted into the identified closest human frameworks respectively to generate humanized antibody clone. In this process, antibody 10G1 and 1C2 were humanized by grafting the CDRs from the murine antibody V-regions onto human germline antibody V-region frameworks, the CDRs grafted from the donor to the acceptor sequence are as defined by Kabat (Kabat et al., 1987). In order to recover the activity of the antibody, a number of framework residues from the murine V-regions that were found to be parts of VH-VL interacting interface or the framework residues acting as “Vernier” zone, which may adjust CDR structure and fine-tune to fit to antigen (Foote et al., 1992) were also retained in the humanized sequence. [0626] The variable domain sequences of the humanized antibodies were summarized in the Table 2B and Table 3B. Example 5: In vitro Assays of Humanized Anti-C5aR1 Antibodies [0627] Generation of recombinant IgG versions of humanized anti-C5aR1 antibodies [0628] The full-length IgG versions of humanized C5aR1 antibodies were generated as described above. [0629] C5a Receptor binding assay: The binding of humanized anti-C5aR1 antibodies to huC5aR1-overexpressing cells was examined as described above in Example 2. EC50 values of the humanized anti-C5aR1 antibodies derived from 1C2 and 10G1 were summarized respectively in Table 9 and Table 10. [0630] The EC50 values of the exemplary humanized antibodies were also shown in Figure 2 and Figure 6. As shown in Figure 2A-2B, the exemplary humanized antibody 1C2.35 exhibited comparable or even better binding activity to C5aR1 as compared to its corresponding chimeric antibody 1C2, and the humanization did not alter its binding function. However, as shown in Figure 6A-6B, the exemplary humanized antibody 10G1.44 exhibited reduced binding activity as compared to its corresponding chimeric antibody. Table 9
Figure imgf000209_0001
Table 10
Figure imgf000209_0002
[0631] C5a ligand binding inhibition assay of humanized antibodies: Expi293cells overexpressing huC5aR1 were plated at 20,000 cells/well.50μL of the individual humanized antibodies at the indicated concentration (typically titrations starting at 100nM decreasing in 5-fold increments) was added to individual well followed by incubation for 30 min at RT. Plates were washed 2 times with FACS buffer, then 50μL FACS buffer containing AlexaFluor 647-labeled human C5a was added to each well and cells were incubated for 10 min at RT. Cells were washed 3 times with FACS buffer and C5a binding as assayed by flow cytometry using BD Accuri C6 or Thermofisher Attune NxT. Mean fluorescent values were recorded at each dilution and plotted as the log[Ab] and IC50 values determined in GraphPad Prism 6.0. [0632] As shown in Figure 3, the exemplary humanized antibody 1C2.35 exhibited comparable inhibitory activity of C5a ligand binding as compared to its corresponding chimeric antibody 1C2, demonstrating that the humanization of the chimeric antibody did not affect its blocking function. [0633] In vitro functional inhibition assays: Assays using the C5aR1-TEV/ E-Arrestin-Luc reporter cells and inhibition of labeled-C5a binding were performed as described above in Example 2. IC50 values of the humanized anti-C5aR1 antibodies derived from 1C2 and 10G1 were summarized respectively in Table 11 and Table 12. [0634] The IC50 values of the exemplary humanized antibodies were also shown in Figure 4. As shown in Figure 4A-4B, the exemplary humanized antibody 1C2.35 exhibited comparable or even better inhibitory activity of C5aR1 function as compared to its corresponding chimeric antibody 1C2 and reference antibody, and the humanization did not affect its inhibition ability of C5aR1 function. Table 11
Figure imgf000210_0001
Table 12
Figure imgf000210_0002
[0635] In vitro human primary neutrophil CD11b upregulation assay: Assays measuring inhibition of C5a-induced CD11b upregulation on primary neutrophils were performed with humanized antibodies as described above in Example 2. The IC50 values of the humanized anti-C5aR1 antibodies derived from 1C2 were summarized in Table 13. [0636] The IC50 values of the exemplary humanized antibodies were also shown in Figure 5 and Figure 7. The results demonstrate that both exemplary humanized antibodies 1C2.35 and 10G1.44 exhibited better inhibitory activity of C5a-induced CD11b upregulation on primary neutrophils as compared to their corresponding chimeric antibodies and reference antibody, and the humanization did not affect their inhibition ability of C5a-induced CD11b upregulation on primary neutrophils. Table 13
Figure imgf000211_0001
Example 6 Affinity maturation of clone 10G1.44. [0637] As humanization of 10G1 reduced its affinity, humanized clone 10G1.44 was selected for affinity maturation via phage display. [0638] Library construction: To generate Fab libraries for affinity maturation, hard randomization strategies were used using NNK walking. Residues at positions 26-30 of LC- CDR1, 89-97 of LC-CDR3, 50-58 of HC-CDR2 and 95-100 of HC-CDR3, were targeted. Phagemid displaying monovalent Fab on the surface of M13 bacteriophage, served as the library template for grafting. The library DNA with homologous ends to linearized phagemid vector was generated through overlap PCR. The phage library was generated according to established protocols and was around 7.1 ×108 transformants in size, as estimated by dilution plating. A number of bacterial colonies were sequenced to check the diversity of the library. [0639] Panning and screening of phage display library: Four to six affinity maturation panning rounds using the above library were carried out. Briefly, 1×1014 phages were pre- incubated with 2×106 Expi293 cells in PBS at RT for 30 min to deplete non-specific binders. Cells were pelleted at 2,000 g for 2 min and the unbound phage containing supernatant was collected and phage numbers were determined by OD.1×1013 unbound phages were then added to 2×106 Expi293 cells overexpressing huC5aR1 that were labeled with carboxyfluorescein succinimidyl amino ester (CFSE). Cells were incubated with the phage for 10 min on ice. After incubation the cells were pelleted at 2,000 g and washed 4-7 times (increasing in number at later panning rounds) with 1× PBS to remove unbound phage. After washing, 8×106 unlabeled Expi293 cells overexpressing huC5aR1 were added to capture fast off-rate phage and the mixture was incubated for 30 min at RT. After incubation, the cells were pelleted at 2,000 g and washed 4 times with 1× PBS and resuspended in 1 ml PBS. Cells were stained for bound phage using biotin-labeled anti-M13 phage protein for 30 min at RT. Cells were washed 2 times with 1× PBS after which cells were incubated with AF647- labeled streptavidin for 30 min at RT. After incubation, the cells were pelleted at 2,000 g and washed 4 times with 1× PBS and resuspended in 5 ml PBS. Cells that were CFSE positive having the strongest bound phage signal were sorted using BD FACS Jazz. Following sorting, bound phage were eluted from the cells and the cells were lysed. Eluted phage and cell lysates were grown overnight at 37ºC in 2YT media with carbenicillin/kanamycin and 1×1010/ml M13KO7 helper phage. Binding to C5aR1 of the resulting pool was performed via flow cytometry. Positive clones were selected and grown overnight for DNA purification and sequencing according to the manufacture protocols known in the field. The variable domain sequences of the affinity matured antibodies were summarized in the Table 2C and Table 3C. [0640] Generation of IgG1 versions of affinity matured anti-C5aR1 antibody derived from 10G1.44 and subsequent recombinant IgG molecules purification were performed as described above in Example 3. [0641] C5a Receptor binding assay: The binding of affinity matured anti-C5aR1 antibodies to huC5aR1-overexpressing cells was examined as described above in Example 2. EC50 values of the affinity matured anti-C5aR1 antibodies derived from 10G1.44 were summarized in Table 14. [0642] As shown in Table 14, the exemplary affinity matured anti-C5aR1 antibodies exhibited highly better binding activity to C5aR1 as compared to their parental antibody 10G1.44, demonstrating that the affinity maturation of C5aR1 antibody markedly improved the binding function. Table 14
Figure imgf000213_0001
[0643] In vitro blocking assays of affinity matured antibodies: FACS based C5a ligand binding inhibition assay of affinity matured antibodies were performed as described above in Example 5. The IC50 values of exemplary affinity matured antibodies derived from 10G1.44 were summarized in Table 15. [0644] As shown in Table 15, the exemplary affinity matured anti-C5aR1 antibodies 10G1.44.1, 10G1.44.3, 10G1.44.4.10G1.44.5, 10G1.44.6 and 10G1.44.7 exhibited good inhibitory activity of C5a ligand binding. Table 15
Figure imgf000213_0002
[0645] In vitro functional assays of Affinity Matured antibodies: Assays using the C5aR1- TEV/E-Arrestin-Luc reporter cells and inhibition of labeled-C5a binding were performed as described above in Example 2. The IC50 values of exemplary affinity matured anti-C5aR1 antibodies derived from 10G1.44 were summarized in Table 16. [0646] As shown in Table 16, the exemplary affinity matured anti-C5aR1 antibodies exhibited highly improved inhibitory activity of C5aR1 function as compared to their parental antibody 10G1.44, demonstrating that the affinity maturation of C5aR1 antibody markedly improved the inhibitory function. Table 16
Figure imgf000214_0001
[0647] In vitro human primary neutrophil CD11b upregulation assay: Assays measuring inhibition of C5a-induced CD11b upregulation on primary neutrophils were performed with affinity matured antibodies as described above. The IC50 values of exemplary affinity matured anti-C5aR1 antibodies derived from 10G1.44 were summarized in Table 17. [0648] As shown in Table 17, the exemplary affinity matured anti-C5aR1 antibodies 10G1.44.110G1.44.2, 10G1.44.3, 10G1.44.4, 10G1.44.5, 10G1.44.6 and 10G1.44.7 could effectively inhibit C5a-iduced upregulation of neutrophil CD11b. Table 17
Figure imgf000214_0002
Example 7 In vivo efficacy Studies [0649] Prophylactic imiquimod-induced psoriasis model: The murine model of imiquimod- induced psoriasis was utilized to demonstrate in vivo anti-autoimmune efficacy. Mice of 8–12 weeks are pretreated i.p. with 10 mg/kg of the exemplary antibody 1C2, 10G1, reference antibody (InnatePharma) or non-relevant control IgG for 2 hr before imiquimod (IMQ) dosing on day 0. Mice were subsequently treated with daily topical doses (62.5mg) of commercially available IMQ cream (5%; Si-Chuan Med-Shine Pharmaceutical, H20030128, Chengdu, Sichuan, China) for six days. Naive group represents wild type mouse as control. Body weight, ear thickness, dermal scaling and redness are scored daily (PASI score). Skin tissue is collected at day 6 and analyzed by histology for dermal thickening. [0650] The results of FIGS.8A-8D show the in vivo anti-autoimmune efficacy results of exemplary anti-C5aR1 antibody 1C2 in murine model of imiquimod-induced psoriasis. FIG.8A shows the H&E staining results for skin thickness and scales from psoriatic skin lesions samples after treatment of exemplary anti-C5aR1 antibody 1C2 or reference antibody. FIG.8B shows the epidermal thickness quantification result from psoriatic skin lesions samples after treatment of exemplary anti-C5aR1 antibody 1C2 or reference antibody. FIG.8C shows the psoriasis area severity index (PASI) total score result of exemplary anti- C5aR1 antibody 1C2 or the reference antibody after IMQ treatment. FIG.8D shows a schematic diagram of experimental protocol including prophylactic anti-C5aR1 antibody treatment, followed by disease induction by IMQ treatment and collection and recording of the parameters during and after the experiment. [0651] As shown in Figure 8A-8C, the exemplary antibody 1C2 exhibited comparable reduction of skin thickness, scales and PASI total score from psoriatic skin lesions as compared to the reference Ab, demonstrating that the exemplary antibody 1C2 prevented inflammation and tissue destruction equally well compared to the reference Ab. The exemplary anti-C5aR1 antibody 10G1 also exhibited prevention of inflammation and tissue destruction in murine model of imiquimod-induced psoriasis (data not shown). Example 8 Anti-tumor therapy [0652] Subcutaneous Tumor Models: MC38 [0653] A summary of the subcutaneous tumor model studies was shown in Table 18 (below). TABLE 18: Summary of in vivo subcutaneous tumor study protocol
Figure imgf000216_0001
[0654] Animals and husbandry: Female huC5aR1-Tg mice (7-9 weeks of age) (Biocytogen) were used in the studies. The animals were fed irradiated Harlan 2918.15 Rodent Diet and water ad libitum. Animals were ear tagged for identification purposes and shaved on the left dorsal flank area in preparation of cell implantation. Animals were housed in Innovive disposable ventilated caging with corn cob bedding at 60 complete air changes per hour. The environment was controlled to a temperature range of 70°±2°F and a humidity range of 30- 70%. All procedures carried out in this experiment were conducted by skilled personnel in compliance with all the laws, regulations and guidelines of the National Institutes of Health (NIH). [0655] Cell preparation and implantation: MC38 cells were obtained from ATCC and cultured according to manufacture protocols known in the field. The cells were suspended in Dulbecco’s Phosphate Buffered Saline (DPBS) at a concentration of 5×106/ml. Test animals were sterilized at the implantation site with an alcohol prep pad and were implanted subcutaneously in 0.1 mL using a 25-gauge needle and 1 mL syringe. [0656] Measurements and antibody treatment: Tumors were allowed to grow and the mouse were then randomized into study groups. Mice were distributed to ensure that the mean body weights for all groups were within 10% of the overall mean tumor burden for the study population. Mice received twice weekly i.p. injections 10 mg/kg of each antibody treatment for 3 weeks and tumor volumes were monitored (n=10 mice/group). Group 1 received IgG1 isotype control (synthesized in house) antibody, and group 2 received 1C2.35 antibody, group 3 received 10G1.44 antibody, group 4 received 10G1.44.1 antibody, group 5 received 10G1.44.6 antibody.

Claims

CLAIMS 1. An isolated anti-C5aR1 antibody, comprising a heavy chain variable domain (VH) comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising SYWMN (SEQ ID NO: 1); an HC-CDR2 comprising RIDPX1X2X3X4TRYNQKFED (SEQ ID NO: 72), wherein X1 is G, R, S, or Y, X2 is D, R, or S, X3 is G or S, and X4 is E or G; and an HC-CDR3 comprising FVX1PX2GX3FX4Y (SEQ ID NO: 73), wherein X1 is I or W, X2 is L, M, Q, S, or V, X3 is A or G, and X4 is A or Q; and a light chain variable domain (VL) comprising: a light chain complementarity determining region (LC-CDR) 1 comprising RSSX1X2X3X4HSNGX5TYLH (SEQ ID NO: 74), wherein X1 is Q or R, X2 is Q or S, X3 is L or P, X4 is L or V, and X5 is N or Q; an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52); and an LC-CDR3 comprising X1QSTX2VPPT (SEQ ID NO: 75), wherein X1 is M or S, and X2 is F, H, L, R, V, or Y.
2. The isolated anti-C5aR1 antibody of claim 1, wherein the anti-C5aR1 antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, or a variant thereof comprising up to about 3 amino acid substitutions; an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 8-15, or a variant thereof comprising up to about 3 amino acid substitutions; and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 24-31, or a variant thereof comprising up to about 3 amino acid substitutions; and a VL comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 39-44, or a variant thereof comprising up to about 3 amino acid substitutions; an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NO: 52, or a variant thereof comprising up to about 3 amino acid substitutions; and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 58-64, or a variant thereof comprising up to about 3 amino acid substitutions.
3. The isolated anti-C5aR1 antibody of claim 1^2, wherein the anti-C5aR1 antibody comprises: (i) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 24, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (ii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 25, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (iii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (iv) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (v) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 28, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (vi) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 29, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 60, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (vii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (viii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 26, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 61, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (ix) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 62, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (x) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 63, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (xi) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (xii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 64, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; or (xiii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 59, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
4. The isolated anti-C5aR1 antibody of any one of claims 1-3, comprising: a VH comprising the amino acid sequence of any one of SEQ ID NOs: 76-91, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 76-91; and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 104-120, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 104-120.
5. The isolated anti-C5aR1 antibody of any one of claims 1-4, comprising: (i) a VH comprising the amino acid sequence of SEQ ID NO: 76, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 76; and a VL comprising the amino acid sequence of SEQ ID NO: 104, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 104; (ii) a VH comprising the amino acid sequence of SEQ ID NO: 77, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 77; and a VL comprising the amino acid sequence of SEQ ID NO: 105, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 105; (iii) a VH comprising the amino acid sequence of SEQ ID NO: 78, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; and a VL comprising the amino acid sequence of SEQ ID NO: 106, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 106; (iv) a VH comprising the amino acid sequence of SEQ ID NO: 79, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 79; and a VL comprising the amino acid sequence of SEQ ID NO: 107, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 107; (v) a VH comprising the amino acid sequence of SEQ ID NO: 80, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 80; and a VL comprising the amino acid sequence of SEQ ID NO: 106, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 106; (vi) a VH comprising the amino acid sequence of SEQ ID NO: 81, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 81; and a VL comprising the amino acid sequence of SEQ ID NO: 108, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 108; (vii) a VH comprising the amino acid sequence of SEQ ID NO: 82, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 82; and a VL comprising the amino acid sequence of SEQ ID NO: 109, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 109; (viii) a VH comprising the amino acid sequence of SEQ ID NO: 83, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 83; and a VL comprising the amino acid sequence of SEQ ID NO: 110, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 110; (ix) a VH comprising the amino acid sequence of SEQ ID NO: 83, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 83; and a VL comprising the amino acid sequence of SEQ ID NO: 111, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 111; (x) a VH comprising the amino acid sequence of SEQ ID NO: 84, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 84; and a VL comprising the amino acid sequence of SEQ ID NO: 112, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 112; (xi) a VH comprising the amino acid sequence of SEQ ID NO: 85, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 85; and a VL comprising the amino acid sequence of SEQ ID NO: 113, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 113; (xii) a VH comprising the amino acid sequence of SEQ ID NO: 86, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 86; and a VL comprising the amino acid sequence of SEQ ID NO: 107, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 107; (xiii) a VH comprising the amino acid sequence of SEQ ID NO: 87, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 87; and a VL comprising the amino acid sequence of SEQ ID NO: 114, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 114; (xiv) a VH comprising the amino acid sequence of SEQ ID NO: 88, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 88; and a VL comprising the amino acid sequence of SEQ ID NO: 115, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 115; (xv) a VH comprising the amino acid sequence of SEQ ID NO: 89, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 89; and a VL comprising the amino acid sequence of SEQ ID NO: 116, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 116; (xvi) a VH comprising the amino acid sequence of SEQ ID NO: 90, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 90; and a VL comprising the amino acid sequence of SEQ ID NO: 117, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 117; (xvii) a VH comprising the amino acid sequence of SEQ ID NO: 91, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 91; and a VL comprising the amino acid sequence of SEQ ID NO: 118, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 118; (xviii) a VH comprising the amino acid sequence of SEQ ID NO: 89, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 89; and a VL comprising the amino acid sequence of SEQ ID NO: 119, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 119; or (xix) a VH comprising the amino acid sequence of SEQ ID NO: 89, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 89; and a VL comprising the amino acid sequence of SEQ ID NO: 120, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 120.
6. The isolated anti-C5aR1 antibody of claim 1-5, wherein the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of the VH comprising the amino acid sequence of any one of SEQ ID NOs: 76-91; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of the VL comprising the amino acid sequence of any one of SEQ ID NOs: 104-120.
7. The isolated anti-C5aR1 antibody of claim 1-6, wherein the anti-C5aR1 antibody comprises^ (i) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 76; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 104; ^ (ii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 78; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 106; ^ (iii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 79; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 107; ^ (iv) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 80; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 106; ^ (v) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 81; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 108; ^ (vi) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 82; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 109; ^ (vii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 83; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 110; ^ (viii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 83; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 111; ^ (ix) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 84; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 112; ^ (x) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 85; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 113; ^ (xi) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 86; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 107; ^ (xii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 87; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 114; or^ (xiii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 88; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 115.
8. An isolated anti-C5aR1 antibody, comprising a heavy chain variable domain (VH) comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising SGYSWH (SEQ ID NO: 2), or a variant thereof comprising up to about 3 amino acid substitutions; an HC-CDR2 comprising YIHSSGDTDYNPSLKR (SEQ ID NO: 16), or a variant thereof comprising up to about 3 amino acid substitutions; and an HC-CDR3 comprising SIGDY (SEQ ID NO: 32), or a variant thereof comprising up to about 3 amino acid substitutions; and a light chain variable domain (VL) comprising:: a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 45), or a variant thereof comprising up to about 3 amino acid substitutions; an LC-CDR2 comprising KVSNRFS (SEQ ID NO: 52), or a variant thereof comprising up to about 3 amino acid substitutions; and an LC-CDR3 comprising SQSTHVPWT (SEQ ID NO: 65), or a variant thereof comprising up to about 3 amino acid substitutions.
9. The isolated anti-C5aR1 antibody of claim 8, comprising: a VH comprising the amino acid sequence of any one of SEQ ID NOs: 92-96, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 92-96; and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 121-127, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 121-127.
10. The isolated anti-C5aR1 antibody of any one of claims 8-9, comprising: (i) a VH comprising the amino acid sequence of SEQ ID NO: 92, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 92; and a VL comprising the amino acid sequence of SEQ ID NO: 121, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 121; (ii) a VH comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 93; and a VL comprising the amino acid sequence of SEQ ID NO: 122, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 122; (iii) a VH comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 93; and a VL comprising the amino acid sequence of SEQ ID NO: 123, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 123; (iv) a VH comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 93; and a VL comprising the amino acid sequence of SEQ ID NO: 124, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 124; (v) a VH comprising the amino acid sequence of SEQ ID NO: 94, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 94; and a VL comprising the amino acid sequence of SEQ ID NO: 125, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 125; (vi) a VH comprising the amino acid sequence of SEQ ID NO: 95, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 95; and a VL comprising the amino acid sequence of SEQ ID NO: 126, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 126; (vii) a VH comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 96; and a VL comprising the amino acid sequence of SEQ ID NO: 127, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 127; (viii) a VH comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 96; and a VL comprising the amino acid sequence of SEQ ID NO: 124, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 124; (ix) a VH comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 96; and a VL comprising the amino acid sequence of SEQ ID NO: 125, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 125; or (x) a VH comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 96; and a VL comprising the amino acid sequence of SEQ ID NO: 126, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 126.
11. The isolated anti-C5aR1 antibody of any one of claims 8-10, wherein the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of the VH comprising the amino acid sequence of any one of SEQ ID NOs: 92-96; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of the VL comprising the amino acid sequence of any one of SEQ ID NOs: 121-127.
12. The isolated anti-C5aR antibody, wherein the anti-C5aR antibody comprises: (i) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (ii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (iii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (iv) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (v) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 48, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (vi) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 49, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; (vii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 50, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs; or (viii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant thereof comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71, or a variant thereof comprising up to about 5 amino acid substitutions in the LC-CDRs.
13. The isolated anti-C5aR1 antibody of claim 12, comprising: a VH comprising the amino acid sequence of any one of SEQ ID NOs: 97-103, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 97-103; and a VL comprising the amino acid sequence of any one of SEQ ID NOs: 128-135, or a variant thereof having at least about 80% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 128-135.
14. The isolated anti-C5aR1 antibody of any one of claims 12-13, comprising: (i) a VH comprising the amino acid sequence of SEQ ID NO: 97, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 97 and a VL comprising the amino acid sequence of SEQ ID NO: 128, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 128; (ii) a VH comprising the amino acid sequence of SEQ ID NO: 98, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 98 and a VL comprising the amino acid sequence of SEQ ID NO: 129, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 129; (iii) a VH comprising the amino acid sequence of SEQ ID NO: 99, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 99 and a VL comprising the amino acid sequence of SEQ ID NO: 130, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 130; (iv) a VH comprising the amino acid sequence of SEQ ID NO: 100, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 100 and a VL comprising the amino acid sequence of SEQ ID NO: 131, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 131˗^ (v) a VH comprising the amino acid sequence of SEQ ID NO: 101, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 101 and a VL comprising the amino acid sequence of SEQ ID NO: 132, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 132˗^ (vi) a VH comprising the amino acid sequence of SEQ ID NO: 102, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 102 and a VL comprising the amino acid sequence of SEQ ID NO: 133, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 133˗^ (vii) a VH comprising the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 103 and a VL comprising the amino acid sequence of SEQ ID NO: 134, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 134; or^ (viii) a VH comprising the amino acid sequence of SEQ ID NO: 102, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 102 and a VL comprising the amino acid sequence of SEQ ID NO: 135, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 135.
15. The isolated anti-C5aR1 antibody of any one of claims 12-14, wherein the anti-C5aR1 antibody comprises a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of the VH comprising the amino acid sequence of any one of SEQ ID NOs: 97-103; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of the VL comprising the amino acid sequence of any one of SEQ ID NOs: 128-135.
16. The isolated anti-C5aR1 antibody of any one of claims 12-15, wherein the anti-C5aR1 antibody comprises: (i) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 97; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 128; (ii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 98; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 129; (iii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 99; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 130; (iv) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 100; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 131; (v) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 101; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 132; (vi) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 102; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 133; (vii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 103; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 134; or (viii) a VH comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 102; and a VL comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 135.
17. An isolated anti-C5aR1 antibody that specifically binds to C5aR1 competitively with the isolated anti-C5aR1 antibody of any one of claims 1-16, or specifically binds to the same epitope as the isolated anti-C5aR1 antibody of any one of claims 1-16.
18. The isolated anti-C5aR1 antibody of any one of claims 1-17, wherein the anti-C5aR1 antibody binds to the C5aR1 with a Kd from about 0.1 pM to about 1 nM.
19. The isolated anti-C5aR1 antibody according to any one of claims 1-18, wherein the anti- C5aR1 antibody comprises an Fc fragment.
20. The isolated anti-C5aR1 antibody of claim 19, wherein the anti-C5aR1 antibody is a full- length IgG antibody.
21. The isolated anti-C5aR1 antibody of claim 20, wherein the anti- C5aR1 antibody is a full- length IgG1, IgG2, IgG3 or IgG4 antibody.
22. The isolated anti-C5aR1 antibody of any one of claims 1-21, wherein the anti-C5aR1 antibody is chimeric, human, or humanized.
23. The isolated anti-C5aR1 antibody according to any one of claims 1-18, wherein the anti- C5aR1antibody is an antigen binding fragment selected from the group consisting of a Fab, a Fab’, a F(ab)’2, a Fab’-SH, a single-chain Fv (scFv), an Fv fragment, a dAb, a Fd, or a diabody.
24. An isolated nucleic acid molecule that encodes the isolated anti-C5aR1 antibody according to any one of claims 1-23.
25. A vector comprising the nucleic acid molecule of claim 24.
26. An isolated host cell comprising the isolated anti-C5aR1 antibody of any one of claims 1- 23, the isolated nucleic acid of claim 24, or the vector of claim 25.
27. A method of producing an isolated anti-C5aR1 antibody, comprising: a) culturing the host cell of claim 26 under conditions effective to express the anti- C5aR1 antibody; and b) obtaining the expressed anti-C5aR1 antibody from the host cell.
28. A pharmaceutical composition comprising the anti-C5aRl antibody according to any one of claims 1-23, the nucleic acid of claim 24, the vector of claim 25, or the isolated host cell of claim 26, and a pharmaceutically acceptable carrier.
29. A method of treating a disease or condition in an individual in need thereof, comprising administering to the individual an effective amount of the anti-C5aRl antibody according to any one of claims 1-23, the nucleic acid of claim 24, the vector of claim 25, the isolated host cell of claim 26, the antibody produced according to claim 27 or the pharmaceutical composition of claim 28.
30. The metiiod of claim 29, wherein the disease or condition is an inflammatory diseases, autoimmune disease, or cancers, optionally the disease or condition is associated with C5aRl signaling.
31. The metiiod of claim 30, wherein the disease or condition is selected from allergy, atherogenesis, anaphylaxis, malignancy, chronic and acute inflammation, histamine and IgE-mediated allergic reactions, shock, and rheumatoid arthritis, atherosclerosis, multiple sclerosis, allograft rejection, fibrotic disease, asthma, inflammatory glomerulopathies.
PCT/US2022/082260 2021-12-29 2022-12-22 ANTIBODIES SPECIFICALLY RECOGNIZING C5aR1 AND USES THEREOF WO2023129870A2 (en)

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