Method of treating conditions, reducing an inflammatory response, or improving organ function in a subject having a corona virus infection by administering an inhibitor of C5a activity

1 . A method of treating a subject having a medical condition caused by or associated with infection with a corona virus, the method comprising;

administering to a subject in need thereof an effective amount of an inhibitor of C5a activity, wherein the medical condition caused by or associated with infection with a corona virus is pneumonia, fever, or a combination thereof; wherein the inhibitor of C5a activity is a protein ligand that specifically binds to C5, or to C5a, or to a C5a receptor and wherein the corona virus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

2 . The method of claim 1 , wherein the subject suffers from COVID-19.

3 . The method of claim 1 , wherein administering the inhibitor of C5a to the subject results in one or more of the following:

reduction of C-reactive protein;

reduction of fever;

increase of lymphocyte counts in blood;

reducing ALT/AST; and/or

increase of oxygen index (PaO 2 /FiO 2 ).

4 . The method of claim 1 , wherein administering the inhibitor of C5a activity to the subject:

lowers the concentration of C5;

inhibits cleavage of C5 into C5a and C5b;

lowers the concentration of C5a;

inhibits binding between C5a and a C5a receptor;

lowers the concentration of a C5a receptor; and/or

inhibits the activity of a C5a receptor.

5 . The method of claim 1 , wherein the protein ligand comprises

an antibody or an antigen-binding fragment thereof.

6 . The method of claim 1 , wherein the inhibitor of C5a activity reduces expression of C5 protein or a C5a receptor protein.

7 . The method of claim 4 , wherein the C5a receptor is C5aR and/or C5L2.

8 . The method of claim 1 , wherein the inhibitor of C5a activity is selected from the group consisting of:

(a) MEDI-7814, ALXN-1007, or NOX-D21, or an antigen-binding fragment thereof;

(b) an antibody or an antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof competes with one of the antibodies indicated under (a) for binding to C5a;

(c) Eculizumab, ALXN1210, ALXN5500, or LFG316, or an antigen-binding fragment thereof;

(d) an antibody or an antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof competes with one of the antibodies indicated under (c) for binding to C5;

(e) Nomacopan or RA101495;

(f) an antibody or an antigen-binding fragment thereof or a protein or a macrocyclic peptide wherein said antibody or antigen-binding fragment thereof or protein or macrocyclic peptide competes with one of the proteins or peptides indicated under (e) for binding to C5;

(g) Avacincaptad pegol;

(h) an antibody or an antigen-binding fragment thereof or an aptamer, wherein said antibody or antigen-binding fragment thereof or aptamer competes with Avacincaptad pegol for binding to C5;

(i) AMY-201 or Mirococept;

(j) an antibody or an antigen-binding fragment thereof or a protein wherein said antibody or antigen-binding fragment thereof or protein competes with one of the proteins indicated under (i) for binding to C3b;

(k) Bikaciomab;

(l) an antibody or an antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof competes with Bikaciomab for binding to Factor B;

(m) Lampalizumab;

(n) an antibody or an antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof competes with Lampalizumab for binding to Factor D;

(o) ALN-CC5;

(p) Avacopan or a compound according to formula II or formula III; or PMX-53 or a compound according to formula IV;

(q) an antibody or an antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof competes with avacopan or PMX-53 for binding to C5aR;

(r) clone S5/1 or clone 7H110, or an antigen-binding fragment thereof; and

(s) an antibody or an antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof competes with one of the antibodies indicated under (r) for binding to C5aR.

9 . The method of claim 1 , wherein the inhibitor of C5a activity specifically binds to a conformational epitope formed by amino acid sequences NDETCEQRA (SEQ ID NO: 2) and SHKDMQL (SEQ ID NO: 3) of human C5a, and wherein the inhibitor of C5a binds to at least one amino acid within the amino acid sequence according to SEQ ID NO: 2 and to at least one amino acid within the amino acid sequence according to SEQ ID NO: 3.

10 . The method of claim 1 , wherein the inhibitor of C5a activity is an antibody or an antigen-binding fragment thereof, comprising

(i) a variable heavy chain with an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 34 and a variable light chain sequence with an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 35, wherein the variable heavy chain and the variable light chain comprise the amino acid sequences set forth in SEQ ID NOs: 6, 8, 10, 12, 14 and 16 of the light and heavy chain CDR1 to CDR3; or

(ii) a variable heavy chain sequence with an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 36 and the variable light chain sequence with an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 37, wherein the variable heavy chain and the variable light chain comprise the amino acid sequences set forth in SEQ ID NO: 7, 9, 11, 13, 15 and 17 of the light and heavy chain CDR1 to CDR3.

11 . A method of reducing an inflammatory response in a subject suffering from a corona virus infection, the method comprising:

administering to the subject an effective amount of an inhibitor of C5a activity to reduce the inflammatory response in the subject suffering from a corona virus infection; wherein the inhibitor of C5a activity is a protein ligand that specifically binds to C5, or to C5a, or to a C5a receptor and wherein the corona virus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

12 . A method of improving organ function in a subject suffering from a corona virus infection, the method comprising:

administering to the subject an effective amount of an inhibitor of C5a activity to improve organ function in the subject suffering from a corona virus infection; wherein lung and/or hepatic organ function is improved in the subject; wherein the inhibitor of C5a activity is a protein ligand that specifically binds to C5, or to C5a, or to a C5a receptor and wherein the corona virus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).