Method of treating a disorder with a c5a inhibitor

Abstract

The present invention is related to a C5a binding agent for use in a method for treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a.

Description

[0001] Aptarion biotech AGA 10083 PCTMethod of treating a disorder with a C5a inhibitor The present invention is related to a C5a binding agent for use in a method of treating and / or preventing a disease, and to a C5a binding agent for use in a method for reducing an adverse effect or for reducing the risk of an adverse effect of an anti-C5a therapy, and a packaging comprising a C5a binding agent.The complement system is part of the body’s innate immune defence system against infections.Invading pathogens trigger a proteolytic cascade that results in the tagging and elimination ofthe microbial intruders and orchestrates immunological and inflammatory processes (Ricklin etal. 2010). Important terminal effector mechanisms are mediated by complement C5 cleavageproducts C5a and C5b which have distinct biological functions in the complement system.C5a acts as a pro-inflammatory factor with enhancing effects on leukocyte recruitment and activation, vascular permeability, and coagulation. With regard to microbial invasion, C5a is produced in order to attract leukocytes to a site of microbial invasion and activivate leukocytes locally. In certain conditions, C5a causes more damage than benefit, for example: ^in sepis and systemic inflammatory response (SIRS) where shock due to plamaextravasation, endothelial glycocalyx shedding, and microcirculation disturbance due to disseminated intravascular coagulation may be observed;^ in pneumonia where pleural effusion and lung edema may be oserved; and^ in ischemia / reperfusion injury where postoperative kidney damage may be observed.Because of that, C5a is an interesting target for treating such conditions.C5b has an immediate anti-bacterial effect by initiating the formation of the membrane attackcomplex (MAC, also known as Terminal Complement Complex, TCC) consisting of C5b, C6, C7, C8 and C9 (also known as or referred to as ‘C5b-9’), a multiprotein complex that formspores in bacterial cell membranes and viral envelopes (Ricklin et al., 2010; Schiela et al., 2018). Because of that important function of C5b, the function of C5b and / or formation of C5b (bycleavage of C5 into C5a and C5b) should not be hampered by any therapy targeting thecomplement system.Blocking cleavage of C5 into C5a and C5b is associated with a risk of infections, such asmeningococcal infections, and sepsis as the most serious side effects (McNamaraet al., 2017;Socie et al., 2019) due to hampering the formation of the membrane attack complex (MAC)consisting of C5b, C6, C7, C8 and C9 (‘C5b-9’). Such blocking has been shown for the C5binding monoclonal antibody eculizumab (McNamaraet al., 2017; Socie et al., 2019).In contrast to the C5 binding antibody eculizumab, selective C5a inhibitors do not interfere with C5 cleavage and formation of the membrane attack complex (MAC). Different types of selective C5a inhibitors are known.A first type of selective C5a inhibitors binds to C5a and C5 without interfering with C5cleavage. Representative examples of this first type of selective C5a inhibitors are C5a bindingnucleic acid molecules such as AON-D21 (also referred to as NOX-D21) and others asdescribed in the international patent applications WO2009 / 040113, WO2010 / 108657 andWO2013104540. Such nucleic acid molecules specifically bind to a target molecule, such asC5a, through a mechanism different from Watson Crick base pairing and are also known as L-aptamers. L-aptamers (also referred to as Spiegelmers) consist of L-nucleotides and are, amongother aptamers, described in ‘The Aptamer Handbook’ (ed. Klussmann, 2006).A second type of selective C5a inhibitors binds to C5a, but does not bind to C5, thereby notinterfering with C5 cleavage. A representative example of this second type of selective C5ainhibitors is the recombinant chimeric monoclonal IgG4 antibody vilobelimab.A third type of selective C5a inhibitors binds to the C5a receptor, thereby not interfering withC5 cleavage. A representative example of this third type of selective C5a inhibitors is the C5areceptor antagonist avacopan (Bekker et al., 2016).A selective C5a inhibitor of the first type that binds to both C5a and C5 (such as C5a bindingnucleic acid molecule AON-D21 and others) is conofronted with the problem that the level of C5 in blood of both healthy individuals and individuals suffering from a disease associated with or caused by C5a is comparable, i.e. about 455 nM (mean concentration; corresponding to 84.5µg / L) (Zelek et al., 2020). In contrast thereto, the titer of C5a in blood of both healthyindividuals and individuals suffering from a disease associated with or caused by C5a issignificantly lower compared to the titer of C5 and is below 3.0 nM (corresponding to 25 µg / ml)in healthy individuals (Zelek et al., 2020), and is in the range of 5.2 nM (mean concentration; corresponding to 43.0 µg / L)in individuals suffering from a disease associated with or caused by C5a, for example COVID-19 (Zelek et al., 2020).Due to the above-described high surplus of C5 compared to C5a in blood of a subject, a personskilled in the art expects that most of the administered molecules of the first type of selectiveC5a inhibitors will bind to C5 and will hardly be available for binding to and thus inhibitingC5a, if one dose or several doses of the selective C5a inhibitor are administered to a subject andsuch dosage regimen results in similar levels of the selective C5a inhibitor and C5 in thesubject’s blood (or even lower levels of the selective C5a inhibitor), provided that the bindingconstant of the selective C5a inhibitor for C5a and C5 is in the same range. Under suchconditions, only a small or no effect of such selective C5a inhibitor on C5a function is expected.Increasing the doses of the selective C5a inhibitor is typically not an option with regard to costsand a potentially high risk of side effects during treatment.The elimination half-life for IgG1, IgG2 and IgG4 antibodies is approx. 18 - 21 days, which issubstantially longer that the half-life of other proteins with similar weight (Ryman andMeibohm, 2017). Such longer half-life may result in treament-emergent adverse events(TEAEs) as shown in a study using C5a binding antibody vilobelimab for patients with SARS-Co V-2 infection (Vlaar et al., 2022). In said study, the patients with SARS-Co V-2 infectionreceived standard of care or vilobelimab at a dose of 800 mg intraveneously for a maximum ofsix dosis and observed treatment-emergent adverse events (TEAEs) were as follows: pneumonia (38 [21,7%] vs 26 [14,8%]), herpes simplex (11 [6,3%] vs 5 [2,6%]),Staphylococcus pneumonia (10 [5,7%] vs 5 [2,6%]) and Herpes simplex reactivation (4 [2,3%]vs 2 [1,1%]). It is strongly assumed that the TEAEs resulted from a prolonged blockade of C5aafter end of treatment due to high terminal half-life as known for antibodies in the human bodyand / or the high dosis of Vilobelimab used, thereby suppressing or diminishing C5a’s positive role in the defense against infections based on microbial invasion for a lengthy period of time after end of treatment.The problem underlying the present invention is the provision of a means for use in a methodfor treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administerting a C5a inhibitor to the subject. A further problem underlying the present invention is the provision of means for use in a method for treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, and wherein the method comprises administering a C5a inhibitor to the subject, wherein the C5a inhibitor binds to both C5a and C5. A still further problem underlying the present invention is the provision of a means for use in a method for treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering to the subject a C5a inhibitor, and wherein the method shows fewer side effects, preferably fewer side effects caused by the C5a inhibitor. These and other problems underlying the present invention are solved by the subject matter of the attached independent claims. Preferred embodiments may be taken from the dependent claims. These and other problems underlying the present invention are also solved by the followingembodiments and aspects.Embodiment 1. A C5a binding agent for use in a method of treating and / or preventing adisease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering to the subject multiple doses of the C5a binding agent at alevel, preferably a trough level, of the C5a binding agent of 80 to 300 nM in the blood of thesubject.Embodiment 2. The C5a binding agent for use of Embodiment 1, wherein the multipledoses comprise a first dose, at least a second dose and optionally one or more subsequent dose(s).Embodiment 3. The C5a binding agent for use of any one of Embodiments 1 to 2, whereinthe trough level of the C5a binding agent is the level of the C5a binding agent in the blood of the subject before administering a or the second dose of the C5a binding agent and / or one or more of an or of the optional one or more subsequent dose(s) of the C5a binding agent.Embodiment 4. The C5a binding agent for use of any of Embodiments 1, 2 and 3, whereinat the trough level of the C5a binding agent of about 100 to 300 nM or at a level of the C5abinding agent in the blood of the subject of ≥ about 100 nM 100% of an activity of C5a in theblood of the subject is inhibited, wherein preferably at the trough level of the C5a binding agent of 100 to 300 nM or at a level of the C5a binding agent in the blood of the subject of ≥ 100 nM100% of an activity of C5a in the blood of the subject is inhibited.Embodiment 5. The C5a binding agent for use of any one of Embodiments 1, 2, 3 and 4,wherein the trough level of the C5a binding agent is about 100 nM in the blood of the subject, preferably the trough level of the C5a binding agent is 100 nM in the blood of the subject.Embodiment 6. The C5a binding agent for use of any of Embodiments 1, 2 and to 3,wherein at the trough level of the C5a binding agent of about 100 nM or at a level of the C5a binding agent in the blood of the subject of about 100 nM 100% of an activity of C5a in the blood of the subject is inhibited, preferably at the trough level of the C5a binding agent of 100 nM or at a level of the C5a binding agent in the blood of the subject of 100 nM 100% of an activity of C5a in the blood of the subject is inhibited.Embodiment 7. The C5a binding agent for use of any of Embodiments 1, 2 and 3, whereinat the trough level of the C5a binding agent of 80 nM or at a level of the C5a binding agent inthe blood of the subject of about 80 nM at least 80% of an activity of C5a in the blood of thesubject is inhibited.Embodiment 8. The C5a binding agent for use of any of Embodiments 1, 2 and 3, whereinat the trough level of the C5a binding agent of about 90 nM or at a level of the C5a bindingagent in the blood of the subject of 90 nM at least 90% of an activity of C5a in the blood of the subject is inhibited.Embodiment 9. A C5a binding agent for use in a method of treating and / or preventing adisease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering to the subject multiple doses of the C5a binding agent at a level of the C5a binding agent in the blood of the subject of 80 to 300 nM.Embodiment 10. The C5a binding agent for use of cl Embodiment 9, wherein the multipledoses comprise a first dose, at least a second dose and optionally one or more subsequent dose(s).Embodiment 11. The C5a binding agent for use of any of Embodiments 9 to 10, whereinthe level of the C5a binding agent is the level of the C5a binding agent in the blood of the subject before administering the a or the second dose of the C5a binding agent and / or wherein the level of the C5a binding agent is the level of the C5a binding agent in the blood of the subject before administering one or more of an or of the optional one or more subsequent dose(s) of the C5a binding agent.Embodiment 12. The C5a binding agent for use of any of Embodiments 9, 10 and 11,wherein at a level of the C5a binding agent in the blood of the subject of ≥ about 100 nM 100% of an activity of C5a is inhibited, wherein preferably at a level of the C5a binding agent in the blood of the subject of ≥ 100 nM 100% of an activity of C5a in the blood of the subject is inhibited.Embodiment 13. The C5a binding agent for use of any of Embodiments 9, 10, 11 and 12,wherein the method comprises administering to the subject multiple doses of the C5a binding agent at the level of the C5a binding agent in the blood of the subject of about100 nM, preferably the method comprises administering to the subject multiple doses of the C5a binding agent at the level of the C5a binding agent in the blood of the subject of 100 nM.Embodiment 14. The C5a binding agent for use of any of Embodiments 9, 10, 11, 12 and13, wherein at a level of the C5a binding agent in the blood of the subject of about 100 nM 100 % of an activity of C5a is inhibited, preferably at a level of the C5a binding agent in the bloodof the subject of 100 nM 100 % of an activity of C5a in the blood of the subject is inhibited.Embodiment 15. The C5a binding agent for use of any of Embodiments 9, 10 and 11,wherein at a level of the C5a binding agent in the blood of the subject of about 80 nM at least 80 % of an activity of C5a in the blood of the subject is inhibited.Embodiment 16. The C5a binding agent for use of any of Embodiments 9, 10 and 11,wherein at a level of the C5a binding agent in the blood of the subject of about 90 nM at least 90 % of an activity of C5a in the blood of the subject is inhibited.Embodiment 17. A C5a binding agent for use in a method of treating and / or preventing adisease in a subject, wherein the disease is associated with or caused by C5a, wherein themethod comprises administering to the subject the C5a binding agent during a treatment period, wherein the administering of the C5a binding agent provides a level of the C5a binding agent in the blood of the subject, wherein the level of the C5a binding agent in the blood of the patient isa) a minimum level of 80 to 300 nM maintained during the treatment period of thesubject; or b) a minimum level of 80 to 300 nM at the end of the treatment period of the subject.Embodiment 18. The C5a binding agent for use of Embodiment 17, wherein the minimumlevel is reached within the treatment period, preferably the minimum level is reached within the treatment period at one or several points in time. Embodiment 19. The C5a binding agent for use of any of Embodiments 17 to 18, wherein multiple doses of the C5a binding agent are administered during the treatment period.Embodiment 20. The C5a binding agent for use of Embodiment 19, wherein the multipledoses comprise a first dose, at least a second dose and optionally one or more subsequent dose(s).Embodiment 21. The C5a binding agent for use of any of Embodiments 19 to 20, whereinif multiple doses of the C5a binding agent are administered, the minimum level of the C5a binding agent is the level of the C5a binding agent in the blood of the subject before administering a or the second dose of the C5a binding agent and / or the minimum level of the C5a binding agent is the level of the C5a binding agent in the blood of the subject beforeadministering one or more of an or of the optional one or more subsequent dose(s) of the C5abinding agent.Embodiment 22. The C5a binding agent for use of any of Embodiments 17, 18, 19, 20 and21, wherein at a level of the C5a binding agent in the blood of the subject of ≥ about 100 nM100% of an activity of C5a in the blood of the subject is inhibited, wherein preferably at a level of the C5a binding agent in the blood of the subject of ≥ 100 nM 100% of an activity of C5a in the blood of the subject is inhibited.Embodiment 23. The C5a binding agent for use of any of Embodiments 17, 18, 19, 20, 21and 22, wherein the minimum level of the C5a binding agent in the blood of the subject is about100 nM, preferably the minimum level of the C5a binding agent in the blood of the subject is100 nM.Embodiment 24. The C5a binding agent for use of any of Embodiments17, 18, 19, 20, 21and 22, wherein at the minimum level of the C5a binding agent in the blood of the subject ofabout 100 nM 100% of an activity of C5a in the blood of the subject is inhibited, whereinpreferably at the minimum level of the C5a binding agent in the blood of the subject of 100 nM100% of an activity of C5a in the blood of the subject is inhibited.Embodiment 25. The C5a binding agent for use of any of Embodiments 17, 18, 19, 20 and21, wherein at the minimum level of the C5a binding agent in the blood of the subject of about80 nM at least 80% of an activity of C5a in the blood of the subject is inhibited.Embodiment 26. The C5a binding agent for use of any of Embodiments 17, 18, 19, 20 and21, wherein at the minimum level of the C5a binding agent in the blood of the subject of about90 nM at least 90% of an activity of C5a in the blood of the subject is inhibited.Embodiment 27. The C5a binding agent for use of any one of Embodiments 17, 18, 19,20, 21, 22, 23, 24, 25 and 26, wherein the treatment period of the subject starts with the administering of a first dose of the C5a binding agent and ends at the time at which the level ofthe C5a binding agent in the blood of the subject falls or is below 80 – 300 nM after a last dose of the C5a binding agent was administered, preferably the treatment period of the subject starts with the administering of a first dose of the C5a binding agent and ends at the time at which thelevel of the C5a binding agent in the blood of the subject falls or is below 80 – 100 nM afterthe last dose of the C5a binding agent was administered, wherein more preferably the treatment period of the subject starts with the administering of a or the first dose of the C5a binding agent and ends at the time at which the level of the C5a binding agent in the blood of the subject falls or is below about 100 nM after the last dose of the C5a binding agent was administered, wherein most preferably the treatment period of the subject starts with administering of a or the first dose of the C5a binding agent and ends at the time at which the level of the C5a binding agent in the blood of the subject falls or is below 100 nM after the last dose of the C5a binding agent was administered.Embodiment 28. The C5a binding agent for use of any one of Embodiments1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 and 27, wherein anadverse effect or a risk for an adverse effect upon administering the C5a binding agent to thesubject is reduced or avoided.Embodiment 29. The C5a binding agent for use of Embodiment 28, wherein the adverseeffect is associated with or caused by administering a C5a binding agent to the subject.Embodiment 30. The C5a binding agent for use of any one of Embodiments 28 to 29,wherein the adverse effect is selected from the group comprising of lung edema, pneumonia, herpes simplex, Staphylococcus pneumonia and Herpes simplex reactivation.Embodiment 31. The C5a binding agent for use of any one of Embodiments 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 and 30, wherein the C5a binding agent has a blood plasma half-life of about 6 hours to about 15 hours within the first 12 to 48 hours.Embodiment 32. A C5a binding agent for use in a method for treating and / or preventing adisease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering the C5a binding agent to the subject, wherein an activity ofC5a in the blood of the subject is reduced by 50% or less within or for a priod of about 24 toabout 72 hours after administering the C5a binding agent to the subject.Embodiment 33. The C5a binding agent for use of Embodiment 32, wherein an adverseeffect or a risk for an adverse effect of or upon administering the C5a binding agent to thesubject is reduced or avoided.Embodiment 34. The C5a binding agent for use of Embodiment 33, wherein the adverseeffect is associated with or caused by administering the C5a binding agent to the subject, preferably the adverse effect is caused by or associated with the or a C5a binding agent..Embodiment 35. The C5a binding agent for use of any one of Embodiments 33 to 34,wherein the adverse effect is selected from the group comprising of lung edema, pneumonia, herpes simplex, Staphylococcus pneumonia and Herpes simplex reactivation.Embodiment 36. The C5a binding agent for use of any one of Embodiments 32, 33, 34 and35, wherein the C5a binding agent used has a blood plasma half-life of about 6 hours to about 15 hours within the first 12 to 48 hours, preferablyafter administering the C5a binding agent to the subject as determined in the blood of the subject. Embodiment 37. A C5a binding agent for use in a method for treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the treating and / or preventing comprises administering the C5a binding agent to the subject, wherein the treating and / or preventing of the disease is associated with or goes along with a reduced adverse effect or a reduced risk of an adverse effect, wherein the adverse effect is caused by or arising from the administering of the C5a binding agent, wherein an activity of C5a in the blood of the subject is reduced by 50 % or less within or for a priod of about 24 to about 72 hours after administering the C5a binding agent to the subject.Embodiment 38. The C5a binding agent for use of Embodiment 37, wherein the adverseeffect is selected from the group comprising of lung edema, pneumonia, herpes simplex, Staphylococcus pneumonia and Herpes simplex reactivation.Embodiment 39. The C5a binding agent for use of any one of Embodiments 37 to 38,wherein the C5a binding agent used has a plasma half-life of about 6 hours to about 15 hours within the first 12-48 hours after administering the C5a binding agent to the subject as determined in the blood of the subject. Embodiment 40. A C5a binding agent for use in a method for treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the treating and / or preventing comprises administering the C5a binding agent to the subject, wherein the treating and / or preventing of the disease is associated with or goes along with a reduced adverse effect or a reduced risk of an adverse effect, wherein the adverse effect is caused by or arising from the administering of the C5a binding agent, wherein the C5a binding agent has plasma half-life of about 6 hours to about 15 hours within the first 12 to 48 hours after administering the C5a binding agent to the subject as determined in the blood of the subject.Embodiment 41. The C5a binding agent for use of Embodiment 40, wherein the adverseeffect is selected from the group comprising of lung edema, pneumonia, herpes simplex, Staphylococcus pneumonia and Herpes simplex reactivation. Embodiment 42. A C5a binding agent for use in a method for reducing an adverse effect or for reducing the risk of an adverse effect of an anti-C5a therapy administered to a subject, wherein the method comprises administering to the subject a C5a binding agent, wherein an activity of C5a in the blood of the subject is reduced by 50 % or less within or for a priod of about 24 to about 72 hours after administering the C5a binding agent to the subject.Embodiment 43. The C5a binding agent for use of Embodiment 42, wherein an adverseeffect or a risk for an adverse effect of an anti-C5a therapy is reduced or avoided.Embodiment 44. The C5a binding agent for use of Embodiment 43, wherein the adverseeffect is associated with or caused by the anti-C5a therapy.Embodiment 45. The C5a binding agent for use of any one of Embodiments 43 to 44,wherein the adverse effect is selected from the group comprising of lung edema, pneumonia, herpes simplex, Staphylococcus pneumonia and Herpes simplex reactivation.Embodiment 46. The C5a binding agent for use of any one of Embodiments 42, 43, 44 and45, wherein the anti-C5a therapy comprises administering a C5a binding agent to the subject.Embodiment 47. The C5a binding agent for use of any one of Embodiments 42, 43, 44,45and 46, wherein the C5a binding agent used in the anti-C5a therapy has a plasma half-life of about 6 hours to about 15 hours within the first 12 to 48 hours after administering the C5a binding agent to the subject as determined in the blood of the subject. Embodiment 48. A C5a binding agent for use in a method for reducing an adverse effect or for reducing the risk of an adverse effect of an anti-C5a therapy administered to a subject, wherein the method comprises administering to the subject a C5a binding agent, wherein the C5a binding agent has a plasma half-life of about 6 hours to about 15 hours within the first 12 to 48 hours after administering the C5a binding agent to the subject hours as determined in the blood of the subject.Embodiment 49. The C5a binding agent for use of Embodiment 48, wherein an adverseeffect or a risk for an adverse effect of an anti-C5a therapy is reduced or avoided.Embodiment 50. The C5a binding agent for use of Embodiment 49, wherein the adverseeffect is associated with or caused by the anti-C5a therapy.Embodiment 51. The C5a binding agent for use of any one of Embodiments 49 to 50,wherein the adverse effect is selected from the group comprising of lung edema, pneumonia, herpes simplex, Staphylococcus pneumonia and Herpes simplex reactivation.Embodiment 52. The C5a binding agent for use of any one of Embodiments 48. 49, 50 and51, wherein the anti-C5a therapy comprises administering a C5a binding agent to the subject.Embodiment 53. The C5a binding agent for use of any of Embodiments 32, 33, 34, 35, 36,37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 and 52, wherein the level of the C5a binding agent in the blood of the subject falls below or is less than about 100 nM within 8 to 24 hours after a last dose of the C5a binding agent has been administered to the subject, preferably the concentration of the C5a binding agent in the blood of the subject falls below or is less than 100 nM within 8 to 24 hours after a last dose of the C5a binding agent has been administered to the subject.Embodiment 54. The C5a binding agent according for use of Embodiments1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52 and 53, wherein the C5a binding agent is administered to the subject according to a dosage regimen in which successive doses of the C5a binding agent are administered to the subject.Embodiment 55. The C5a binding agent for use of Embodiment 54, wherein the dosageregimen comprises administering the C5a binding agent every 48 hours, 24 hours, 12 hours or 8 hours.Embodiment 56. The C5a binding agent for use of any one of Embodiments 54 and 55,wherein the dosage regimen comprises administering the C5a binding agent by continuousadministration, wherein preferably the continuous administration comprises administering a loading dose at the beginning.Embodiment 57. The C5a binding agent for use of any of Embodiments 54, 55 and 56,wherein the dosage regimen comprises administering the C5a binding agent by intravenous administration, subcutaneous administration or administration by inhalation.Embodiment 58. The C5a binding agent for use of any of Embodiments 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 and 57, wherein the blood is full blood, blood plasma or blood serum, preferably plasma.Embodiment 59. A C5a binding agent for use in a method of treating and / or preventing adisease in a subject, wherein the disease is which is associated with or caused by C5a, wherein the method comprises administering to the subject a) a total amount of 4.18 to 220.25 nmol of the C5a binding agent per kg bodyweight ofthe subject over a period of 8 to 48 hours, or b) a total amount of 0.055 to 2.9 mg of the C5a binding agent per kg bodyweight of thesubject over a period of 8 to 48 hours.Embodiment 60. The C5a binding agent for use of Embodiment 59, wherein the methodcomprises administering to the subject a) a total amount of 12.53 to 72.12 nmol of the C5a binding agent per kg bodyweight ofthe subject every day, or b) a total amount of 0.165 to 0.95 mg of the C5a binding agent per kg bodyweight of thesubject every day.Embodiment 61. The binding agent for use of any of Embodiments 59 and 60, wherein themethod comprises administering to the subject a) 98.73 to 220.25 nmol of the C5a binding agent per kg body weight of the subject everytwo days, b) 25.82 to 72.12 nmol of the C5a binding agent per kg body weight of the subject everyday, c) 9.11 to 35.70 nmol of the C5a binding agent per kg body weight of the subject twice aday, d) 9.11 to 35.7 nmol of the C5a binding agent per kg body weight of the subject three timesa day, e) 1.3 to 2.9 mg of the C5a binding agent per kg body weight of the subject every twodays, f) 0.34 to 0.95 mg of the C5a binding agent per kg body weight of the subject every day,g) 0.12 to 0.47 mg of the C5a binding agent per kg body weight of the subject twice a day,or h) 0.055 to 0.32 mg of the C5a binding agent per kg body weight of the subject three timesa day.Embodiment 62. The C5a binding agent for use of anyone Embodiments 59, 60 and 61,wherein the method comprises administering to the subject multiple doses of the C5a bindingagent at a trough level of the C5a binding agent of 80 to 300 nM in the blood of the subject, wherein preferably blood is whole blood, blood plasma or blood serum, wherein more preferably blood is blood plasma.Embodiment 63. The C5a binding agent for use of Embodiment 62, wherein the multipledoses comprise a first dose, at least a second dose and optionally one or more subsequent dose(s).Embodiment 64. The C5a binding agent for use of any one Embodiments 62 to 63, whereinthe trough level of the C5a binding agent is the level of the C5a binding agent in the blood of the subject before administering a or the second dose of the C5a binding agent and / or one or more of an or of the optional one or more subsequent dose(s) of the C5a binding agent.Embodiment 65. The C5a binding agent for use of any of Embodiment 62, 63 and 64,wherein at the trough level of the C5a binding agent of about 100 to 300 nM or at a level of the C5a binding agent in the blood of the subject of ≥ about 100 nM 100% of an activity of C5a in the blood of the subject is inhibited, wherein preferably at the trough level of the C5a binding agent of 100 to 300 nM or at a level of the C5a binding agent in the blood of the subject of ≥ 100 nM 100% of an activity of C5a in the blood of the subject is inhibited.Embodiment 66. The C5a binding agent for use of any one of Embodiments 62, 63, 64 and65, wherein the trough level of the C5a binding agent is about 100 nM in the blood of the subject, preferably the trough level of the C5a binding agent is 100 nM in the blood of the subject.Embodiment 67. The C5a binding agent for use of any of Embodiments 62, 63, 64, 65 and66, wherein at the trough level of the C5a binding agent of about 100 nM or at a level of the C5a binding agent in the blood of the subject of about 100 nM 100% of an activity of C5a in the blood of the subject is inhibited, preferably at the trough level of the C5a binding agent of 100 nM or at a level of the C5a binding agent in the blood of the subject of 100 nM 100% of an activity of C5a in the blood of the subject is inhibited.Embodiment 68. The C5a binding agent for use of any of Embodiment 62, 63, 64, 65, 66and 67, wherein at the trough level of the C5a binding agent of 80 nM or at a level of the C5abinding agent in the blood of the subject of 80 nM at least 80% of an activity of C5a in theblood of the subject is inhibited.Embodiment 69. The C5a binding agent for use of any of Embodiments 62, 63, 64, 65, 66,67 and 68, wherein at the trough level of the C5a binding agent of 90 nM or at a level of the C5a binding agent in the blood of the subject of 90 nM at least 90% of an activity of C5a in the blood of the subject is inhibited.Embodiment 70. The C5a binding agent for use of any of Embodiments 62, 63, 64, 65, 66,67, 68 and 69, wherein a) the trough level is reached after at least two to four doses of the dosage regimens, and / orb) the trough level is reached after the first dose the dosage regimens and beforeadministering the second dose according to dosage regimens.Embodiment 71. The binding agent for use of Embodiment 59, wherein, wherein themethod comprises administering to the subject a) a total amount of 7.59 to 220.25 nmol of the C5a binding agent per kg bodyweight ofthe subject over a period of 8 to 48 hours, or b) a total amount of 0.1 to 2.9 mg of the C5a binding agent per kg bodyweight of thesubject over a period of 8 to 48 hours.Embodiment 72. The C5a binding agent for use of Embodiment 59, wherein the methodcomprises administering to the subject a) a total amount of 22.78 to 72.15 nmol of the C5a binding agent per kg bodyweight ofthe subject every day, or b) a total amount of 0.3 to 0.95 mg of the C5a binding agent per kg bodyweight of thesubject every day.Embodiment 73. The binding agent for use of any of Embodiments 71 and 72, wherein themethod comprises administering to the subject a) 102.53 to 220.25 nmol of the C5a binding agent per kg body weight of the subject everytwo days, b) 29.62 to 72.15 nmol of the C5a binding agent per kg body weight of the subject everyday, c) 12.15 to 35.70 nmol of the C5a binding agent per kg body weight of the subject twice aday, d) 7.59 to 24.3 nmol of the C5a binding agent per kg body weight of the subject three timesa day,e) 1.35 to 2.9 mg of the C5a binding agent per kg body weight of the subject every twodays, f) 0.39 to 0.95 mg of the C5a binding agent per kg body weight of the subject every day,g) 0.16 to 0.47 mg of the C5a binding agent per kg body weight of the subject twice a day,or h) 0.1 to 0.32 mg of the C5a binding agent per kg body weight of the subject three times aday.Embodiment 74. The C5a binding agent for use of any one of Embodiments 71 to 72,wherein the method comprises administering to the subject multiple doses of the C5a binding agent at a trough level of the C5a binding agent of 80 to 300 nM in the blood of the subject, wherein preferably blood is whole blood, blood plasma or blood serum, wherein more preferably blood is blood plasma.Embodiment 75. The C5a binding agent for use of Embodiment 74, wherein the multipledoses comprise a first dose, at least a second dose and optionally one or more subsequent dose(s).Embodiment 76. The C5a binding agent for use of any one of Embodiments 74 to 75wherein the trough level of the C5a binding agent is the level of the C5a binding agent in the blood of the subject before administering a or the second dose of the C5a binding agent and / or one or more of an or of the optional one or more subsequent dose(s) of the C5a binding agent.Embodiment 77. The C5a binding agent for use of any of Embodiments 74, 75 and 76,wherein at the trough level of the C5a binding agent of about 100 to 300 nM or at a level of the C5a binding agent in the blood of the subject of ≥ about 100 nM 100% of the activity of C5a is inhibited, wherein preferably at the trough level of the C5a binding agent of 100 to 300 nM or at a level of the C5a binding agent in the blood of the subject of ≥ 100 nM 100% of the activity of C5a is inhibited.Embodiment 78. The C5a binding agent for use of any one of Embodiment 74, 75, 76 and77, wherein the trough level of the C5a binding agent is about 100 nM in the blood of the subject, preferably the trough level of the C5a binding agent is 100 nM in the blood of the subject.Embodiment 79. The C5a binding agent for use of any of Embodiments 74, 75, 76, 77 and78, wherein at the trough level of the C5a binding agent of about 100 nM or at a level of the C5a binding agent in the blood of the subject of about 100 nM 100% of an activity of C5a in the blood of the subject is inhibited, preferably at the trough level of the C5a binding agent of 100 nM or at a level of the C5a binding agent in the blood of the subject of 100 nM 100% of an activity of C5a in the blood of the subject is inhibited.Embodiment 80. The C5a binding agent for use of any of Embodiments 74, 75, 76, 77, 78and 79, wherein at the trough level of the C5a binding agent of 80 nM or at a level of the C5a binding agent in the blood of the subject of 80 nM at least 80% of an activity of C5a in the blood of the subject is inhibited.Embodiment 81. The C5a binding agent for use of any of Embodiments 74, 75, 76, 77, 78,79 and 80, wherein at the trough level of the C5a binding agent of 90 nM or at a level of the C5a binding agent in the blood of the subject of 90 nM at least 90% of an activity of C5a in the blood of the subject is inhibited.Embodiment 82. The binding agent for use of any of Embodiments 74, 75, 76, 77, 78, 79,80 and 81, wherein the trough level is reached after the first dose the dosage regimens and before administering the second dose according to dosage regimens.Embodiment 83. The binding agent for use of Embodiment 59, wherein, wherein themethod comprises administering to the subject a) a total amount of 4.18to 205.06 nmol of the C5a binding agent per kg bodyweight ofthe subject over a period of 8 to 48 hours, or b) a total amount of 0.055 to 2.7 mg of the C5a binding agent per kg bodyweight of thesubject over a period of 8 to 48 hours.Embodiment 84. The C5a binding agent for use of Embodiment 83, wherein the methodcomprises administering to the subject a) a total amount of 12.53 to 59.24 nmol of the C5a binding agent per kg bodyweight ofthe subject every day, orb) a total amount of 0.165 to 0.78 mg of the C5a binding agent per kg bodyweight of thesubject every day.Embodiment 85. The binding agent for use of any of Embodiments 83 and 84, wherein themethod comprises administering to the subject a) 98.73 to 205.06 nmol of the C5a binding agent per kg body weight of the subject everytwo days, b) 28.82 to 59.24 nmol of the C5a binding agent per kg body weight of the subject everyday, c) 9.11 to 22.78 nmol of the C5a binding agent per kg body weight of the subject twice aday, d) 4.18 to 11.39 nmol of the C5a binding agent per kg body weight of the subject threetimes a day, e) 1.3 to 2.7 mg of the C5a binding agent per kg body weight of the subject every twodays, f) 0.34 to 0.78 mg of the C5a binding agent per kg body weight of the subject every day,g) 0.12 to 0.3 mg of the C5a binding agent per kg body weight of the subject twice a day,or h) 0.055 to 0.15 mg of the C5a binding agent per kg body weight of the subject three timesa day.Embodiment 86. The C5a binding agent for use of any one of Embodiments 83, 84 and 85,wherein the method comprises administering to the subject multiple doses of the C5a binding agent at a trough level of the C5a binding agent of 80 to 300 nM in the blood of the subject, wherein preferably blood is whole blood, blood plasma or blood serum, wherein more preferably blood is blood plasma.Embodiment 87. The C5a binding agent for use of Embodiment 86, wherein the multipledoses comprise a first dose, at least a second dose and optionally one or more subsequent dose(s).Embodiment 88. The C5a binding agent for use of any one of Embodiments 86 to 87,wherein the trough level of the C5a binding agent is the level of the C5a binding agent in the blood of the subject before administering a or the second dose of the C5a binding agent and / or one or more of an or of the optional one or more subsequent dose(s) of the C5a binding agent.Embodiment 89. The C5a binding agent for use of any of Embodiments 86, 87 and 88,wherein at the trough level of the C5a binding agent of about 100 to 300 nM or at a level of the C5a binding agent in the blood of the subject of ≥ about 100 nM 100% of an activity of C5a in the blood of the subject is inhibited, wherein preferably at the trough level of the C5a binding agent of 100 to 300 nM or at a level of the C5a binding agent in the blood of the subject of ≥ 100 nM 100% of an activity of C5a in the blood of the subject is inhibited.Embodiment 90. The C5a binding agent for use of any one of Embodiments 86, 87, 88 and89, wherein the trough level of the C5a binding agent is about 100 nM in the blood of the subject, preferably the trough level of the C5a binding agent is 100 nM in the blood of the subject.Embodiment 91. The C5a binding agent for use of any of Embodiments 86, 87, 88, 89 and90, wherein at the trough level of the C5a binding agent of about 100 nM or at a level of the C5a binding agent in the blood of the subject of about 100 nM 100% of an activity of C5a in the blood of the subject is inhibited, preferably at the trough level of the C5a binding agent of 100 nM or at a level of the C5a binding agent in the blood of the subject of 100 nM 100% of an activity of C5a in the blood of the subject is inhibited.Embodiment 92. The C5a binding agent for use of any of Embodiments 86, 87, 88, 89, 90and 91, wherein at the trough level of the C5a binding agent of 80 nM or at a level of the C5abinding agent in the blood of the subject of 80 nM at least 80% of an activity of C5a in the blood of the subject is inhibited.Embodiment 93. The C5a binding agent for use of any of Embodiments 86, 87, 88, 89, 90,91 and 92, wherein at the trough level of the C5a binding agent of 90 nM or at a level of the C5a binding agent in the blood of the subject of 90 nM at least 90% of an activity of C5a in the blood of the subject is inhibited.Embodiment 94. The C5a binding agent for use of any of Embodiments 86, 87, 88, 89, 90,91, 92 and 93, wherein the trough level is reached after at least two to four doses of the dosage regimens.Embodiment 95. The C5a binding agent for use of any of Embodiments 57, 58, 59, 60, 61,62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86,87, 88, 89, 90, 91, 92, 93 and 94, wherein the method comprises administering to the subject a) 121.5 nmol of the C5a binding agent per kg body weight of the subject every two days,b) 37.97 nmol of the C5a binding agent per kg body weight of the subject every day,c) 15.19 nmol of the C5a binding agent per kg body weight of the subject twice a day,d) 9.11 nmol of the C5a binding agent per kg body weight of the subject three times a day,e) 1.6 mg of the C5a binding agent per kg body weight of the subject every two days,f) 0.5 mg of the C5a binding agent per kg body weight of the subject every day,g) 0.2 mg of the C5a binding agent per kg body weight of the subject twice a day, orh) 0.12 mg of the C5a binding agent per kg body weight of the subject three times a day,Embodiment 96. The C5a binding agent for use of any of Embodiments 57, 58, 59, 60, 61,62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94 and 95, wherein the method comprises administering to the subject 15.19 nmol of the C5a binding agent per kg body weight of the subject twice a day. or 0.2 mg of the C5a binding agent per kg body weight of the subject twice a day.Embodiment 97. The C5a binding agent for use of Embodiment 96, wherein the troughlevel is reached after the first dose the dosage regimens and before administering the second dose, and wherein the trough level of the C5a binding agent is about 100 nM in the blood of the subject, preferably the trough level of the C5a binding agent is 100 nM in the blood of the subject.Embodiment 98. The C5a binding agent for use of any one of Embodiments 96 and 97,wherein the trough level is reached after the first dose the dosage regimens and before administering the second dose, and the trough level of the C5a binding agent is 100 to 200 nM in the blood of the subject.Embodiment 99. The binding agent for use of any one of Embodiments 59, 60, 61, 62, 63,64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97 and 98, wherein the method comprises administering to thesubject C5a binding agent every two days, wherein every two days means every 42 to 54 hours,wherein preferably every two days means every 44 to 52, wherein more preferably every twodays means every 46 to 50 hours, wherein most preferably every two days means every 48hours.Embodiment 100. The binding agent for use of any one of Embodiments 59, 60, 61, 62, 63,64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 and 99, wherein the method comprises administering to the subject C5a binding agent every day, wherein every day means 20 to 28 hours, wherein preferably every day means every 22 to 26 hours, wherein more preferably every day means every 23 to 25 hours, wherein most preferably every day means every 24 hours.Embodiment 101. The binding agent for use of any of Embodiments 59, 60, 61, 62, 63, 64,65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 and 100, wherein the method comprises administering to the subject C5a binding agent twice a day, wherein twice day means every 10 to 14 hours, wherein preferably twice day means every 11 to 13 hours, wherein more preferably twice day means every 12 hours.Embodiment 102. The binding agent for use of any one of Embodiments 59, 60, 61, 62, 63,64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 and 101, wherein the method comprises administering to the subject C5a binding agent three times a day, wherein three times a day means every 6 to 10 hours, wherein preferably three times day means every 8 hours.Embodiment 103. The binding agent for use of Embodiment 59, wherein the methodcomprises administering to the subject a loading dose of 3.42 to 4.56 nmol of the C5a binding agent per kg body weight of the subject following a total amount of 9.11 to 12.15 nmol the C5a binding agent per kg body weight of the subject administered throughout the day, wherein preferably total amount of 9.11 to 12.15 nmol the C5a binding agent per kg body weight of the subject is administered throughout the day is administered by continuous infusion to the subject.Embodiment 104. The binding agent for use of Embodiment 103, wherein the methodcomprises administering to the subject a loading dose of 4.56 nmol of the C5a binding agent per kg body weight of the subject following a total amount of 12.15 nmol the C5a binding agent per kg body weight of the subject administered throughout the day, wherein preferably total amount of to 12.15 nmol the C5a binding agent per kg body weight of the subject is administered throughout the day is administered by continuous infusion.Embodiment 105. The binding agent for use of Embodiment 59, wherein the methodcomprises administering to the subject a loading dose of 0.045 to 0.06 mg of the C5a binding agent per kg body weight of the subject following a total amount of 0.12 to 0.16 mg the C5a binding agent per kg body weight of the subject administered throughout the day, wherein preferably total amount of 0.12 to 0.16 mg the C5a binding agent per kg body weight of the subject is administered throughout the day is administered by continuous infusion to the subject.Embodiment 106. The binding agent for of Embodiment 105, wherein the methodcomprises administering to the subject a loading dose of 0.06 mg of the C5a binding agent per kg body weight of the subject following a total amount of 0.16 mg the C5a binding agent per kg body weight of the subject administered throughout the day, wherein preferably total amount of 0.16 mg the C5a binding agent per kg body weight of the subject is administered throughout the day is administered by continuous infusion to the subject.Embodiment 107. A C5a binding agent for use in a method for treating and / or preventing adisease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering to the subject several individual doses Df of the C5a bindingagent, wherein a dose Df of the several individual doses Df, preferably each of the severalindividual doses Df, is as follows:Df = Dose x (1 ± v), whereinnmol⁄ kg^^^^ = ^0.0305nmol⁄ L ∙ ^^^^^^^ − 0.324 nmol⁄ kg ^0.0277 nmol⁄ kg ∙ h^ ^ ∙ ^^ (Formula I) wherein Df = dose to be administered (nmol / kg body weight of the subject),I = dosing interval (h),Ctrough = target level of the C5a binding agent in blood of the subject (nmol / L) at steadystate, 0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject.Embodiment 108. The C5a binding agent for use of Embodiment 107, wherein Ctrough isfrom about 80 nmol / L to about 300 nmol / L.Embodiment 109. The C5a binding agent for use of Embodiment 108, wherein Ctrough is 80nmol / L, 90 nmol / L, 100 nmol / L, 200 nmol / L or 300 nmol / L.Embodiment 110. The C5a binding agent for use of any one of Embodiments 107 to 109,wherein Ctrough is from about 80 nmol / L to about 150 nmol / L, preferably Ctrough is about 100 n mol / L.Embodiment 111. The C5a binding agent for use of any one of Embodiments 107 to 110,wherein the dosing interval I is from about 1 hours to about 96 hours.Embodiment 112. The C5a binding agent for use of Embodiment 111, wherein the dosinginterval I is from about 4 hours to about 72 hours.Embodiment 113. The C5a binding agent for use of any one of Embodiments 111 to 112,wherein the dosing interval I is from about 6 hours to about 60 hours.Embodiment 114. The C5a binding agent for use of any one of Embodiments 111 to 113,wherein the dosing interval I is from about 8 to about 48 hours.Embodiment 115. The C5a binding agent for use of any one of Embodiments 107 to 114,wherein in Formula IDf = Dose x (1 ± v),0 ≤ v ≤ 0.1, preferably 0 ≤ v ≤ 0.05.Embodiment 116. The C5a binding agent for use of any one of Embodiments 107 to 115,wherein the C5a binding agent has an initial elimination half-life t1 / 2 within the first 8 to 96hours after administration to a subject of about 5 hours to about 15 hours.Embodiment 117. The C5a binding agent for use of any one of Embodiments 107 to 116,wherein the C5a binding agent has an initial elimination half-life t1 / 2 within the first 12 to 48hours after administration to a subject of about 5 hours to about 15 hours, preferably about 5hours to about 12 hours.Embodiment 118. The C5a binding agent for use of any one of Embodiments 116 to 117,wherein the elimination half-life t1 / 2is dependent on the Cmax and is determined or is as determined at a Cmax of the C5a binding agent from about 90 nmol / L to about 7300 nmol / L,preferably at a Cmax of the C5a binding agent from about 94 nmol / L to about 7280 nmol / L,more preferably at a Cmax of the C5a binding agent from about 94 nmol / L to about 5274nmol / L.Embodiment 119. The C5a binding agent for use of any one of Embodiments 107 to 118,wherein the affinity of the C5a binding agent for C5a is about ≤ 30 nmol / L, preferably about ≤ 8 nmol / L.Embodiment 120. The C5a binding agent for use of any one of Embodiments 107 to 119,wherein the affinity of the C5a binding agent for C5a is as follows: affinity of the C5a binding to C5a ≤ 1 / x of the target level of the C5a binding agent of formula (I), wherein x is ≤ 10, preferably x is ≤ 20.Embodiment 121. The C5a binding agent for use of any one of Embodiments 107 to 120,wherein the method comprises administering an amount of 4 to 210 nmol of the C5a binding agent per kg body weight of the subject to the subject over a period of 8 to 48 hours.Embodiment 122. The C5a binding agent for use of any one of Embodiments 107 to 121,wherein the method comprises administering the C5a binding agent to the subject as follows, a) 95 to 210 nmol of the C5a binding agent per kg body weight of the subject every twodays, b) 25 to 60 nmol of the C5a binding agent per kg body weight of the subject every day,c) 8 to 23 nmol of the C5a binding agent per kg body weight of the subject twice a day,or d) 4 to 15 nmol of the C5a binding agent per kg body weight of the subject three times aday.Embodiment 123. A C5a binding agent for use in a method for treating and / or preventing adisease in a subject, wherein the disease is associated with or caused by C5a, wherein themethod comprises administering to the subject several individual doses Di of the C5a bindingagent, wherein a dose Di of the several individual doses Di, preferably each of the several individual doses Di is as follows:Di = Dose x (1 ± v), wherein (Formula II) wherein Di = dose to be administered (nmol / kg body weight of the subject),I = dosing interval (h),Ctrough = target level of the C5a binding agent in blood of the subject (nmol / L)after the first dose of the C5a binding agent has been administered to the subject, 0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subjectwherein the method comprises administering to the subject only a single dose Ds, the singledose Ds is calculated as follows:Ds = Dose x (1 ± v), wherein^^^^ = ^0.0713 +∙ nmol⁄ kg ∙ h^ ^ ^nmol⁄ L ∙ ^(Formula III) whereinDs = single dose of the C5a binding agent to be administered (nmol / kg body weightof the subject),I = Interval from dosing for which inhibition of elevated C5a shall be present (h),Cmin = minimal concentration of the C5a binding agent in blood of the subject (nmol / L)required for inhibition at the Interval I after Ds has been administered to thesubject, 0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject. Embodiment 124. The C5a binding agent for use of Embodiment 123, wherein CtroughandCmin are each and individually from about 80 nmol / L to about 300 nmol / L.Embodiment 125. The C5a binding agent for use of Embodiment 124, wherein Ctrough andCmin are each and individually 80 nmol / L, 90 nmol / L, 100 nmol / L, 200 nmol / L or 300 nmol / L.Embodiment 126. The C5a binding agent for use of any one of Embodiments 123 to 125,wherein Ctrough and Cmin are each and individually from about 80 nmol / L to about 150 nmol / L,preferably Ctroughis about 100 nmol / L.Embodiment 127. The C5a binding agent for use of any one of Embodiments 123 to 126,wherein the dosing interval I is from about 1 hours to about 96 hours.Embodiment 128. The C5a binding agent for use of Embodiment 127, wherein the dosinginterval I is from about 4 hours to about 72 hours.Embodiment 129. The C5a binding agent for use of any one of Embodiments 127 to 128,wherein the dosing interval I is from about 6 hours to about 60 hours.Embodiment 130. The C5a binding agent for use of any one of Embodiments 127 to 129,wherein the dosing interval I is from about 8 to about 48 hours.Embodiment 131. The C5a binding agent for use of any one of Embodiments 123 to 130,wherein in formula Dose x (1 ± v), 0 ≤ v ≤ 0.1, preferably 0 ≤ v ≤ 0.05.Embodiment 132. The C5a binding agent for use of any one of Embodiment 123 to 131,wherein the C5a binding agent has an initial elimination half-life t1 / 2 within the first 8 to 96hours after administration to a subject of about 5 hours to about 15 hours.Embodiment 133. The C5a binding agent for use of any one of Embodiments 123 to 132wherein the C5a binding agent has an initial elimination half-life t1 / 2 within the first 12 to 48hours after administration to a subject of about 5 hours to about 15 hours, preferably about 5hours to about 12 hours.Embodiment 134. The C5a binding agent for use of any one of Embodiments 132 to 133,wherein the elimination half-life t1 / 2is determined or is as determined at a Cmax of the C5a binding agent from about 90 nmol / L to about 5300 nmol / L, preferably at a Cmax of the C5a binding agent from about 95 nmol / L to about 5275 nmol / L.Embodiment 135. The C5a binding agent for use of any one of Embodiments 123 to 134,wherein the affinity of the C5a binding agent for C5a is about ≤ 30 nmol / L, preferably about ≤ 8 nmol / L.Embodiment 136. The C5a binding agent for use of any one of Embodiments 123 to 135,wherein the affinity of the C5a binding agent for C5a is as follows: affinity of the C5a binding to C5a ≤ 1 / x of the target level of the C5a binding agent of formula (II), wherein x is ≤ 10, preferably x is ≤ 20.Embodiment 137. The C5a binding agent for use of any one of Embodiments 123 to 136,wherein the method comprises administering an amount of 7 to 225 nmol of the C5a binding agent per kg body weight of the subject to the subject over a period of 8 to 48 hours.Embodiment 138. The C5a binding agent for use of any one of Embodiments 123 to 137,wherein the method comprises administering the C5a binding agent to the subject, a) 100 to 225 nmol of the C5a binding agent per kg body weight of the subject every twodays, b) 29 to 75 nmol of the C5a binding agent per kg body weight of the subject every day,c) 12 to 36 nmol of the C5a binding agent per kg body weight of the subject twice a day,or d) 7 to 25 nmol of the C5a binding agent per kg body weight of the subject three times aday.Embodiment 139. A C5a binding agent for use in a method for treating and / or preventing adisease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises, after administration of a loading dose of the C5a binding agent to the subject, continuously administering the C5a binding agent to the subject, wherein a dose for continuous administration Dca isDca = DoseContInf x (1 ± v), wherein^^^^^^^^^^^ = ^. ^^^ ^. ^^^ kg h (Formula IV), wherein DoseContInf = Continuous infusion dose per hour (nmol / kg (body weight of the subject)∙h),Ctarget = target level of the C5a binding agent in blood of the subject (nmol / L) that is oris to be constant over the duration of the continuous administration, 0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject.Embodiment 140. The C5a binding agent for use of Embodiment 139, wherein Ctarget is fromabout 80 nmol / L to about 300 nmol / L.Embodiment 141. The C5a binding agent for use of Embodiment 140, wherein Ctarget is 80nmol / L, 90 nmol / L, 100 nmol / L, 200 nmol / L or 300 nmol / L.Embodiment 142. The C5a binding agent for use of any one of Embodiments 139 to 141,wherein Ctargetis from about 80 nmol / L to about 150 nmol / L, preferably Ctargetis about 100 nmol / L.Embodiment 143. The C5a binding agent for use of any one of Embodiments 139 to 142,whereinin formula Dca = DoseContInf x (1 ± v),0 ≤ v ≤ 0.1, preferably 0 ≤ v ≤ 0.05.Embodiment 144. The C5a binding agent for use of any one of Embodiments 139 to 143,wherein the C5a binding agent has an initial elimination half-life t1 / 2 within the first 8 to 96 hours after administration to a subject of about 5 hours to about 15 hours.Embodiment 145. The C5a binding agent for use of any one of Embodiments 107 to 144,wherein the C5a binding agent has an initial elimination half-life t1 / 2 within the first 12 to 48 hours after administration to a subject of about 5 hours to about 15 hours, preferably about 5hours to about 12 hours.Embodiment 146. The C5a binding agent for use of any one of Embodiment 146 to 147,wherein the elimination half-life t1 / 2is determined or is as determined at a Cmax of the C5a binding agent from about 90 nmol / L to about 5300 nmol / L, preferably at a Cmax of the C5a binding agent from about 95 nmol / L to about 5275 nmol / L.Embodiment 147. The C5a binding agent for use of any one of Embodiments 139 to 146,wherein the affinity of the C5a binding agent for C5a is about ≤ 30 nmol / L, preferably about ≤ 8 nmol / L.Embodiment 148. The C5a binding agent for use of any one of Embodiments 139 to 147,wherein the affinity of the C5a binding agent for C5a is as follows: affinity of the C5a binding to C5a ≤ 1 / x of the target level of the C5a binding agent of formula (III), wherein x is ≤ 10, preferably x is ≤ 20.Embodiment 149. The C5a binding agent for use of any one of Embodiments 139 to 148,wherein the loading dose Doseload= Ctarget / DNCmax,wherein DNCmax is the dose-normalized Cmax calculated as Cmax divided by the applied doseof the C5a binding agent.Embodiment 150. The C5a binding agent for use of Embodiment 149, wherein DNCmax isfrom about 15 (nmol / L) / (nmol / kg body weight of the subject) to about 32 (nmol / L) / (nmol / kg body weight of the subject), preferably DNCmax is from about 15.7 (nmol / L) / (nmol / kg body weight of the subject) to about 31.2 (nmol / L) / (nmol / kg body weight of the subject).Embodiment 151. The C5a binding agent for use of any one of Embodiments 149 to 150,wherein DNCmax is from about 23(nmol / L) / (nmol / kg body weight of the subject) to about 24 (nmol / L) / (nmol / kg body weight of the subject), prefer about 23.4 (nmol / L) / (nmol / kg body weight of the subject).Embodiment 152. The C5a binding agent for use of any one of Embodiments 139 to 151,wherein the method comprises administering to the subject a loading dose of 3 to 13 nmol of the C5a binding agent per kg body weight of the subject.Embodiment 153. The C5a binding agent for use of any one of Embodiments 139 to 151,wherein the method comprises, after administering the loading dose to the subject, administering to the subject a continuous infusion of 0.4 to 1.4 nmol of the C5a binding agent per kg body weight of the subject per hour.Embodiment 154. A C5a binding agent for use in a method for treating and / or preventing adisease in a subject, wherein the disease is associated with or caused by C5a, wherein themethod comprises administering the C5a binding agent to the subject as follows: a) 95 to 225 nmol of the C5a binding agent per kg body weight of the subject every twodays, b) 25 to 75 nmol of the C5a binding agent per kg body weight of the subject every day,c) 8 to 36 nmol of the C5a binding agent per kg body weight of the subject twice a day, ord) 4 to 25 nmol of the C5a binding agent per kg body weight of the subject three times aday.Embdoiemt 155. The C5a binding agent for use of Embodiment 154, wherein a dose of15.19 nmol of the C5a binding agent per kg body weight of the subject is administered to the subject every 11 to 13 hours, preferably every 12 hours.Embodiment 156. The C5a binding agent for use of any one of Embodiments 154 to 155,wherein the C5a binding agent is AON-D21 comprises a nucleotide sequence according to SEQID NO: 92 and is represented by the following structural formula: (structural formula I)wherein NHC6H12O is a hexylamino linker and R is and n is approximately 450, wherein the molecular formula is C398H458N160Na40O287P40[C2H4O]2n, wherein n is approximately 450.Embodiment 157. A C5a binding agent for use in a method of treating a disease in a subject,wherein the disease is associated with or caused by C5a, wherein the subject is suffering from the disease, and wherein the subject has an elevated C5a activity in the blood, wherein the method comprises administering to the subject a dose of the C5a-binding agent, wherein the C5a binding agent administered to the subject inhibits the elevated C5a activity in the blood of the subject to a healthy-state level or below a healthy-state level, wherein the inhibition of the elevated C5a activity is, after a last administration of the C5a binding agent to the subject, effective for 0 hours to 96 hours, preferably for 0 hours to 72 hours.Embodiment 158. The C5a binding agent for use of Embodiment 157, wherein a level ofthe C5a binding agent in the blood of the subject of ≥ about 100 nM is effective in inhibiting the elevated C5a activity in the blood of the subject.Embodiment 159. The C5a binding agent for use of Embodiment 158, whrein the elevatedC5a activity is inhibited by at least 80 %, preferably at least 90 % and more preferably 100 %.Embodiment 160. The C5a binding agent for use of any one of Embodiments 157 to 159,wherein the level of the C5a binding agent is below about 50 nM within about 5 to about 15hours after the level of the C5a binding agent in the blood of the subject is lower than the level effective in inhibiting the elevated C5a activity in the blood of the subject.Embodiment 161. The C5a binding agent for use of Embodiment 160, wherein theinhibition of the elevated C5a activity is 50 % or less, preferably compared to the maximum inhibition realized in the administration of the C5a binding agent.Embodiment 162. The C5a binding agent for use of any one of Embodiments 157 to 161,wherein the level of the C5a binding agent is below about 10 nM in the period of 17 hours to48 hoursEmbodiment 163. The C5a binding agent for use of Embodiment 162, wherein theinhibition of the elevated C5a activity is 10 % or less, preferably compared to the maximum inhibition realized in the administration of the C5a binding agent.Embodiment 164. The C5a binding agent for use of any one of Embodiments 157 to 163,wherein the elevated level of C5a activity is a level of C5a activity associated with or caused by the disease.Embodiment 165. The C5a binding agent for use of any one of Embodiments 157 to 164,wherein the elevated level of C5a activity is a C5a level in the blood of the subject of > 3nM, preferably ≥ 5.2 nM.Embodiment 166. The C5a binding agent for use of claim of any one of Embodiments 157to 165, wherein the level of C5a activity in a state of health is a level of C5a in blood which is characteristic for subjects not suffering from the disease.Embodiment 167. The C5a binding agent for use of any one of Embodiments 157 to 166,wherein the level of C5a activity in a state of health is a level of C5a in blood of a subject ≤ 3 nM.Embodiment 168. The C5a binding agent for use of any one of Embodiments 157 to 167,wherein the dose of the C5a binding agent to be administered to the subject for achieving termination of C5a inhibition is as follows: ^^^ =^ ∙ 0.^1 / 2^^^^^^^^=^^^ 5^^^^^^^^^^^^wherein Cmax= Maximum plasma concentration (nmol / L), Cmin = Minimal plasma concentration required for C5a inhibition (nmol / L),^t = Time (h) from Cmax to Cmin,t1 / 2= Plasma half-life (h), and DNCmax = dose-normalized Cmax calculated as Cmax divided by the applied dose of the C5a binding agent.Embodiment 169. A C5a binding agent for use in a method for treating and / or preventing adisease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering the C5a binding agent to the subject, wherein the method reduces treatment-emergent adverse events (TEAEs) or reduces the risk of treatment-emergent adverse events (TEAEs), wherein the C5a binding agent is AON-D21 comprises a nucleotidesequence according to SEQ ID NO: 92 and is represented by the following structural formula:

[0002] (structural formula I)wherein NHC6H12O is a hexylamino linker and R is and n is approximately 450, wherein the molecular formula is C398H458N160Na40O287P40[C2H4O]2n, wherein n is approximately 450.Embodiment 170. A C5a binding agent for use in a method for treating and / or preventing adisease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering the C5a binding agent to the subject, wherein the method reduces treatment-emergent adverse events (TEAEs) or reduces the risk of treatment-emergent adverse events (TEAEs), wherein the C5a binding agent has an elimination half-life t1 / 2 in the first 12 to 48 hours after administration to a subject of about 5 hours to 15 hours.Embodiment 171. The C5a binding agent for use of Embodiment 170, wherein the affinityof the C5a binding agent for C5a is about ≤ 30 nmol / L, preferably about ≤ 8 nmol / L.Embodiment 172. The C5a binding agent for use of any one of Embodiments 170 to 171,wherein the affinity of the C5a binding agent for C5a is as follows: affinity of the C5a binding to C5a ≤ 1 / x of the target level of the C5a binding agent,wherein x is ≤ 10, preferably x is ≤ 20.Embodiment 173. The C5a binding agent for use of any one of Embodiments 170 to 172,wherein the C5a binding agent is binding to C5a and such binding of the C5a binding agent to C5a does not interfere with C5 cleavage.Embodiment 174. A packaging comprising a C5a binding agent, wherein the packagingcomprises a pharmaceutical composition of the C5a binding agent and information on the useof the pharmaceutical composition, wherein the information comprises dosage or dose of theC5a binding agent, wherein the dosage is as defined in any one of embodiments 1 to 173, preferably any one of embodiments 1 to 156.Embodiment 175. The packaging of Embodiment 174, wherein the pharmaceuticalcomposition is present as a unit dose.Embodiment 176. The packaging of Embodiment 175, wherein the unit dose is suitable foradjustment to subject-specific administration.Embodiment 177. The packaging of any one of Embodiments 175 to 176, wherein the unitdose is a concentrated unit dose.Embodiment 178. The packaging of any one of Embodiments 174 to 177, wherein theinformation is provided by a means selected from the group comprising a package insert, a barcode, a QR code or any link to a database or server providing the information.Embodiment 179. The C5a binding agent for use of Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84,85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107,108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, wherein administering the C5a binding agent comprises administering the C5a binding agent by intravenous administration, subcutaneous administration or administration by inhalation, wherein preferably administering the C5a binding agent is administering the C5a binding agent by intravenous administration.Embodiment 180. The C5a binding agent for use of Embodiment 179, wherein theintravenous administration is an intravenous infusion of a solution of the C5a binding agent, preferably for 15 to 30 minutes.Embodiment 181. The C5a binding agent for use of Embodiment 179, wherein theintravenous administration is an intravenous infusion of a solution of the C5a binding and the C5a binding is administered for a maximum of 10 days.Embodiment 182. The C5a binding agent for use of any one of Embodiments 179, 180 and181, wherein the C5a binding agent is administered in a solution, wherein the solution comprises water, buffer, PBS, glucose solution and / or 4% mannitol / 0.05% EDTA; wherein preferably the glucose solution is 5% glucose solution, wherein more preferably 4%mannitol / 0.05% EDTA is used as a storage solution, wherein most preferably 4%mannitol / 0.05% EDTA is used as a storage solution and the C5a binding agent in the storagesolution is diluted in 5% glucose solution before administration.Embodiment 183. The C5a binding agent for use of any of Embodiments 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106,107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125,126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163,164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181 and182, wherein the disease associated with or caused by C5a is characterized by an increased level of C5a in blood of the subject.Embodiment 184. The C5a binding agent for use of Embodiment 183, wherein the level ofC5a in blood of the subject is increased if the level of C5a is higher than 3 nM.Embodiment 185. The C5a binding agent for use of any one of Embodiments 183 to 184,wherein blood is whole blood, blood plasma or blood serum, preferably blood plasma.Embodiment 186. The C5a binding agent for use of any one of Embodiments 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57,58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82,83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124,125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143,144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181,182, 183, 184 and 185, wherein the disease associated with or caused by C5a is a diseaseselected from the group comprising associated with complement activation and C5a-mediated pathogenic mechanisms, and / or is selected from the group comprising of autoimmune disease, inflammatory disease, systemic inflammatory response syndrome, disease of the eye, ischemia / reperfusion injuries, delayed graft function, transplant rejection, cardiovascular disease, respiratory disease, acute reactions, infectious disease, neurological disease, neurodegenerative disease, fibrotic disease, hematological disease, metabolic disease, tumors and clinical complications associated with complement activation by biomaterials, wherein preferably the systemic inflammatory response syndrome is selected from the group comprising sepsis and secondary damages of trauma or severe burns, wherein preferably the tumour is caner, more preferably lung cancer, and wherein preferably the respiratory disease is pneumonia.Embodiment 187. The C5a binding agent for use of any of Embodiments 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58,59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106,107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125,126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144,145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163,164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185 and 186, wherein the C5a binding agent is capable of binding to C5a and / or C5,preferably capable of binding to C5a and C5.Embodiment 188. The C5a binding agent for use of any of Embodiments 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144,145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163,164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186 and 187, wherein the C5a binding agent is an agent having a binding affinityto C5a with a KDof about 0.1 to 5 nM, preferably 0.1 to 2 nM, more preferably 0.1 to 1.0 nM, and / or the C5a binding agent is an agent having a binding affinity to C5 with a KDof about 0.1 to 5 nM, preferably 0.1 to 2 nM, more preferably 0.1 to 1.0 nM.Embodiment 189. The C5a binding agent for use of any of Embodiments 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186, 187 and 188, wherein the C5a binding agent is an inhibitor of an activitymediated by human C5a, wherein preferably the inhibitor is an antagonist.Embodiment 190. The C5a binding agent for use of Embodiment 189, wherein the C5abinding agent is an inhibitor of an activity mediated by human C5 having an inhibitory constant IC50 of about 0.1 to 5 nM, preferably 0.1 to 2 nM, more preferably 0.1 to 0.5 nM.Embodiment 191. The C5a binding agent for use of any of Embodiments 189 to 190,wherein the C5a binding agent is capable inhibiting C5a activity in the presence of C5.Embodiment 192. The C5a binding agent for use of any of Embodiments 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58,59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144,145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163,164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186, 187, 188, 189, 190 and 191, wherein the C5a binding agent has plasma half-life of about 6 hours to about 15 hours within the first 12 to 48 hours after administering theC5a binding agent to the subject as determined in the blood of the subject.Embodiment 193. The C5a binding agent for use of any of Embodiments 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186, 187, 188, 189, 190, 191 and 192, wherein the C5a binding agent inhibitsC5a activity in a blood sample from the subject in the presence of C5, wherein the blood sample is taken after administering the agent to the subject for at least eight hours, wherein inhibition of C5a activity is selected from the group comprising at least 75 % inhibition, at least 80% inhibition, at least 85% inhibition, at least 90% inhibition, at least 95% inhibition, and 100 % inhibition, wherein 100% inhibition corresponds to the C5a activity measured in an healthy individual.Embodiment 194. The C5a binding agent for use of Embodiment 193, wherein the C5aactivity of a healthy individual is the activity resulting from less than 3 nM C5a in the blood.Embodiment 195. The C5a binding agent for use of Embodiment 194, wherein the blood iswhole blood, blood plasma or blood serum, preferably blood plasma.Embodiment 196. The C5a binding agent for use of any one of Embodiments1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 1122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181,182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194 and 195, wherein the subject is a subject who suffers from a disease or is at risk of suffering from a disease, wherein the disease is associated with or caused by C5a.Embodiment 197. The C5a binding agent for use of Embodiment 196, wherein the diseaseassociated with or caused by C5a is characterized by an increased level of C5a in blood of the subject.Embodiment 198. The C5a binding agent for use of Embodiment 197, wherein the level ofC5a in blood of the subject is increased if the level of C5a is higher than 3 nM.Embodiment 199. The C5a binding agent for use of any one of Embodiments 197, and 198,wherein blood is whole blood, blood plasma or blood serum, preferably blood plasma.Embodiment 1200. The C5a binding agent for use of any one of Embodiments 196, 197, 198and 199, wherein the disease is associated with complement activation and C5a-mediated pathogenic mechanisms, and / or is selected from the group comprising of autoimmune disease, inflammatory disease, systemic inflammatory response syndrome, disease of the eye, ischemia / reperfusion injuries, delayed graft function, transplant rejection, cardiovascular disease, respiratory disease, acute reactions, infectious disease, neurological disease, neurodegenerative disease, fibrotic disease, hematological disease, metabolic disease, tumors and clinical complications associated with complement activation by biomaterials, wherein preferably the systemic inflammatory response syndrome is selected from the group comprising sepsis and secondary damages of trauma or severe burns, wherein preferably the tumour is caner, more preferably lung cancer, and wherein preferably the respiratory disease is pneumonia.Embodiment 201. The C5a binding agent for use of any one of Embodiments 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181,182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196 and 197, wherein theC5a binding agent is selected from the group comprising a C5a binding L-aptamer, a C5a binding aptamer, a C5a binding peptide aptamer, a C5a binding antibody, C5a binding antibody fragment and C5a binding anticalin, preferably a C5a binding L-aptamer.Embodiment 202 The C5a binding agent for use of any one of Embodiments 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124,125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200and 201, wherein the C5a binding agent is selected from the group comprising a C5a bindingL-aptamer, a C5a binding aptamer, a C5a binding peptide aptamer, a C5a binding antibody, C5a binding antibody fragment and C5a binding anticalin, preferably a C5a binding L-aptamer. Embodiment 203. The C5a binding agent for use of Embodiment 202, wherein the C5a binding L-aptamer is a nucleic acid molecule capable of binding to human C5a, optionally comprising a modification, wherein the nucleic acid molecule comprises a central stretch of nucleotides, wherein the central stretch of nucleotides comprises a nucleotide sequence of wherein the nucleic acid molecule comprises a central stretch of nucleotides, wherein the central stretch of nucleotides comprises a nucleotide sequence of5’ AUGn1GGUGKUn2n3RGGGHUGUKGGGn4Gn5CGACGCA 3’ [SEQ ID NO: 61],whereinn1 is U or dU, n2 is G or dG, n3 is A or dA, n4 is U or dU, n5 is U or dU and G, A, U, C, H, K, and R are ribonucleotides, and dU, dG and dA are 2’-deoxyribonucleotides.Embodiment 204. The C5a binding agent for use of Embodiment 203, wherein the centralstretch of nucleotides comprises a nucleotide sequence selected from the group ofa) 5’ AUGn1GGUGUUn2n3AGGGUUGUGGGGn4Gn5CGACGCA 3’ [SEQ ID NO: 62],b) 5’ AUGn1GGUGUUn2n3GGGGUUGUGGGGn4Gn5CGACGCA 3’ [SEQ ID NO: 63],c) 5’ AUGn1GGUGUUn2n3AGGGUUGUUGGGn4Gn5CGACGCA 3’ [SEQ ID NO: 64],d) 5’ AUGn1GGUGGUn2n3AGGGUUGUUGGGn4Gn5CGACGCA 3’ [SEQ ID NO: 65],e) 5’ AUGn1GGUGGUn2n3GGGGUUGUGGGGn4Gn5CGACGCA 3’ [SEQ ID NO: 66],f) 5’ AUGn1GGUGGUn2n3GGGGAUGUGGGGn4Gn5CGACGCA 3’[SEQ ID NO: 67], andg) 5’ AUGn1GGUGUUn2n3GGGGCUGUGGGGn4Gn5CGACGCA 3’ [SEQ ID NO: 68],whereinn1 is U or dU, n2 is G or dG, n3 is A or dA, n4 is U or dU, n5 is U or dU andG, A, U and C are ribonucleotides, and dU, dG and dA are 2’-deoxyribonucleotides.Embodiment 205. The C5a binding agent for use of Embodiment 204, wherein the centralstretch of nucleotides comprises a nucleotide sequence of5’ AUGn1GGUGGUn2n3AGGGUUGUUGGGn4Gn5CGACGCA 3’ [SEQ ID NO: 65] whereinn1 is U or dU, n2 is G or dG, n3 is A or dA, n4 is U or dU, n5 is U or dU andG, A, U and C are ribonucleotides, and dU, dG and dA are 2’-deoxyribonucleotides.Embodiment 206. The C5a binding agent for use of Embodiment 205, wherein the centralstretch of nucleotides comprises a nucleotide sequence selected from the group ofa) 5’ AUGdUGGUGGUGAAGGGUUGUUGGGUGUCGACGCA 3’ [SEQ ID NO: 73],b) 5’ AUGUGGUGGUdGAAGGGUUGUUGGGUGUCGACGCA 3’ [SEQ ID NO: 74],c) 5’ AUGUGGUGGUGdAAGGGUUGUUGGGUGUCGACGCA 3’ [SEQ ID NO: 75],d) 5’ AUGUGGUGGUGAAGGGUUGUUGGGdUGUCGACGCA 3’ [SEQ ID NO: 76],e) 5’ AUGUGGUGGUGAAGGGUUGUUGGGUGdUCGACGCA 3’ [SEQ ID NO: 77],f) 5’ AUGdUGGUGGUGAAGGGUUGUUGGGdUGUCGACGCA 3’ [SEQ ID NO: 78],g) 5’ AUGdUGGUGGUGAAGGGUUGUUGGGUGdUCGACGCA 3’[SEQ ID NO: 79],h) 5’ AUGUGGUGGUGAAGGGUUGUUGGGdUGdUCGACGCA 3’ [SEQ ID NO: 80],i) 5’ AUGdUGGUGGUGAAGGGUUGUUGGGdUGdUCGACGCA 3’[SEQ ID NO: 81],j) 5’ AUGdUGGUGGUdGAAGGGUUGUUGGGdUGdUCGACGCA 3’ [SEQ ID NO: 82],k) 5’ AUGdUGGUGGUGdAAGGGUUGUUGGGdUGdUCGACGCA 3’ [SEQ ID NO: 83],l) 5’ AUGdUGGUGGUdGdAAGGGUUGUUGGGdUGdUCGACGCA 3’ [SEQ ID NO:84], preferably the central stretch of nucleotides is5’ AUGdUGGUGGUGAAGGGUUGUUGGGdUGUCGACGCA 3’ [SEQ ID NO: 78] or5’ AUGdUGGUGGUdGdAAGGGUUGUUGGGdUGdUCGACGCA 3’ [SEQ ID NO: 84].Embodiment 207. The C5a binding agent for use of Embodiment 204, wherein the centralstretch of nucleotides comprises a nucleotide sequence of5’ AUGn1GGUGGUn2n3GGGGUUGUGGGGn4Gn5CGACGCA 3’ [SEQ ID NO: 66],whereinn1 is U or dU, n2 is G or dG, n3 is A or dA, n4 is U or dU, n5 is U or dU andG, A, U and C are ribonucleotides, and dU, dG and dA are 2’-deoxyribonucleotides.Embodiment 208. The C5a binding agent for use of Embodiment 204, wherein the centralstretch of nucleotides comprises a nucleotide sequence of5’ AUGn1GGUGGUn2n3GGGGAUGUGGGGn4Gn5CGACGCA 3’ [SEQ ID NO: 67],whereinn1 is U or dU, n2 is G or dG, n3 is A or dA, n4 is U or dU, n5 is U or dU andG, A, U and C are ribonucleotides, and dU, dG and dA are 2’-deoxyribonucleotides.Embodiment 209. The C5a binding agent for use of Embodiment 204, wherein the centralstretch of nucleotides comprises a nucleotide sequence of5’ AUGn1GGUGUUn2n3AGGGUUGUUGGGn4Gn5CGACGCA 3’ [SEQ ID NO: 64],whereinn1 is U or dU, n2 is G or dG, n3 is A or dA, n4 is U or dU, n5 is U or dU andG, A, U and C are ribonucleotides, and dU, dG and dA are 2’-deoxyribonucleotides.Embodiment 210. The C5a binding agent for use of any one of Embodiments 203, 204, 205,206, 207, 208 and 209, wherein the central stretch of nucleotides consists of ribonucleotidesand 2’-deoxyribonucleotides.Embodiment 211. The C5a binding agent for use of any one of Embodiments 203, 204, 205,207, 208 and 209, wherein the central stretch of nucleotides consists of ribonucleotides.Embodiment 212. The C5a binding agent for use of any one of Embodiments 203, 204, 205,206, 207, 208, 209, 210 and 211, wherein the nucleic acid molecule comprises in 5’->3’ direction a first terminal stretch of nucleotides, the central stretch of nucleotides and a second terminal stretch of nucleotides, wherein the first terminal stretch of nucleotides comprises one to five nucleotides, andthe second terminal stretch of nucleotides comprises one to five nucleotides,preferably the first terminal stretch of nucleotides comprises three to five nucleotides, andthe second terminal stretch of nucleotides comprises three to five nucleotides,more preferably the first terminal stretch of nucleotides comprises three nucleotides, andthe second terminal stretch of nucleotides comprises three nucleotides.Embodiment 213. The C5a binding agent for use of Embodiment 212, wherein the firstterminal stretch of nucleotides comprises a nucleotide sequence of 5’ Z1Z2Z3Z4G 3’ and thesecond terminal stretch of nucleotides comprises a nucleotide sequence of 5’ Z5Z6Z7Z8 Z9 3’,wherein Z1 is G or absent, Z2 is S or absent, Z3 is S or absent, Z4 is B or absent, Z5 is C or dC, Z6 is V or absent, Z7 is S or absent, Z8 is S or absent, Z9 is C or absent, and G, S, B, C, V are ribonucleotides, and dC is a 2’-deoxyribonucleotide, preferably a) Z1 is G, Z2 is S, Z3 is S, Z4 is B, Z5 is C or dC, Z6 is V, Z7 is S, Z8 is S, Z9 is C, orb) Z1 is absent, Z2 is S, Z3 is S, Z4 is B, Z5 is C or dC, Z6 is V, Z7 is S, Z8 is S, Z9 isabsent, orc) Z1 is absent, Z2 is absent, Z3 is S, Z4 is B, Z5 is C or dC, Z6 is V, Z7 is S, Z8 is absent,Z9is absent, ord) Z1 is absent, Z2 is absent, Z3 is absent, Z4 is B, Z5 is C or dC, Z6 is V, Z7 is absent,Z8 is absent, Z9 is absent, ore) Z1 is absent, Z2 is S, Z3 is S, Z4 is B, Z5 is C or dC, Z6 is V, Z7 is S, Z8 is S, Z9 is C,orf) Z1 is absent, Z2 is absent, Z3 is S, Z4 is B, Z5 is C or dC, Z6 is V, Z7 is S, Z8 is S, Z9is C, org) Z1 is absent, Z2 is absent, Z3 is absent, Z4 is B, Z5 is C or dC, Z6 is V, Z7 is S, Z8 isS, Z9 is C, orh) Z1 is absent, Z2 is absent, Z3 is absent, Z4 is absent, Z5 is C or dC, Z6 is V, Z7 is S,Z8is S, Z9is C, ori) Z1 is absent, Z2 is absent, Z3 is S, Z4 is B, Z5 is C or dC, Z6 is V, Z7 is S, Z8 is S, Z9is absent, orj) Z1 is absent, Z2 is absent, Z3 is absent, Z4 is B, Z5 is C or dC, Z6 is V, Z7 is S, Z8 isS, Z9is absent, ork) Z1 is absent, Z2 is absent, Z3 is absent, Z4 is absent, Z5 is C or dC, Z6 is V, Z7 is S,Z8is S, Z9is absent, orl) Z1 is absent, Z2 is S, Z3 is S, Z4 is B, Z5 is C or dC, Z6 is V, Z7 is S, Z8 is absent, Z9is absent, orm) Z1 is absent, Z2 is S, Z3 is S, Z4 is B, Z5 is C or dC, Z6 is V, Z7 is absent, Z8 is absent,Z9is absent, orn) Z1 is absent, Z2 is absent, Z3 is absent, Z4 is absent, Z5 is C, Z6 is V, Z7 is S, Z8 isabsent, Z9 is absent, oro) Z1 is absent, Z2 is absent, Z3 is absent, Z4 is B, Z5 is C or dC, Z6 is V, Z7 is S, Z8 isabsent, Z9 is absent, orp) Z1 is absent, Z2 is absent, Z3 is S, Z4 is B, Z5 is C or dC, Z6 is V, Z7 is absent, Z8 isabsent, Z9is absent, orq) Z1 is absent, Z2 is absent, Z3 is S, Z4 is B, Z5 is C or dC, Z6 is absent, Z7 is absent,Z8 is absent, Z9 is absent.Embodiment 214. The C5a binding agent for use of any one of Embodiments 212 to 213,wherein the first terminal stretch of nucleotides comprises a nucleotide sequence of5’ GCCUG 3’ and the second terminal stretch of nucleotides comprises a nucleotide sequenceof 5’ CAGGC 3’ or of 5’ dCAGGC 3’, whereinC, A, G and U are ribonucleotides, and dC is a 2’-deoxyribonucleotide.Embodiment 215. The C5a binding agent for use of Embodiment 214, wherein the secondterminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCAGGC 3’.Embodiment 216. The C5a binding agent for use of Embodiment 214, wherein the secondterminal stretch of nucleotides comprises a nucleotide sequence of 5’ CAGGC 3’.Embodiment 217. The nucleic acid molecule according to any one of Embodiments 212 to213, whereinthe first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ CCUG 3’ or5’ CUG 3’ or 5’ UG 3’or 5’ G 3’, andthe second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCAGGC 3’,wherein C, A, G and U are ribonucleotides, and dC is a 2’-deoxyribonucleotide.Embodiment 218. The C5a binding agent for use of Embodiment 217, whereinthe first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ CCUG 3’.Embodiment 219. The C5a binding agent for use of Embodiment 217, whereinthe first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ CUG 3’.Embodiment 220. The C5a binding agent for use of Embodiments 212 and 213, whereina) the first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ GCUG 3’ andthe second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCAGC 3’; orb) the first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ GCCG 3’ andthe second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCGGC 3’; orc) the first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ GGCG 3’ andthe second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCGCC 3’;wherein C, A, G and U are ribonucleotides, and dC is a 2’-deoxyribonucleotide.Embodiment 221 The C5a binding agent for use of Embodiment 218, whereinfirst terminal stretch of nucleotides comprises a nucleotide sequence of 5’ GGCG 3’ and thesecond terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCGCC 3’.Embodiment 222. The C5a binding agent for use of any one of Embodiments 223 and 213,whereinthe first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ CUG 3’ or5’ UG 3’or 5’ CG 3’ or 5’ G 3’, andthe second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCAGC 3’,wherein C, A, G and U are ribonucleotides, and dC is a 2’-deoxyribonucleotide.Embodiment 223. The C5a binding agent for use of any one of Embodiments 212 and 213,whereinthe first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ GCUG 3’, andthe second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCAC 3’ or5’ dCC 3’ or 5’ dCA 3’, whereinC, A, G and U are ribonucleotides, and dC is a 2’-deoxyribonucleotide.Embodiment 224. The C5a binding agent for use of any one of Embodiments 212 and 213,wherein a) the first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ GUG 3’and the second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCAC 3’; orb) the first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ UG 3’and the second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCA 3’; orc) the first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ GCG 3’and the second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCGC 3’; ord) the first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ CG 3’ andthe second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCGC 3’; ore) the first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ G 3’ andthe second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCGC 3’; orf) the first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ GCG 3’and the second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCC 3’; org) the first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ GCG 3’and the second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dC 3’; orh) the first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ GG 3’and the second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ dCC 3’;i) the first terminal stretch of nucleotides comprises a nucleotide sequence of 5’ GCG 3’and the second terminal stretch of nucleotides comprises a nucleotide sequence of 5’ CGC 3’; whereinC, A, U and G are ribonucleotides, and dC is a 2’-deoxyribonucleotide.Embodiment 225. The C5a binding agent for use of Embodiment 224, the first terminalstretch of nucleotides comprises a nucleotide sequence of 5’ GCG 3’ and the second terminalstretch of nucleotides comprises a nucleotide sequence of 5’ dCGC 3’.Embodiment 226. The C5a binding agent for use of any one of Embodiments 203, 204, 205,207, 208, 209, 211, 212, 213, 214 and 216, wherein the nucleic acid molecule comprises anucleotide sequence selected from the group of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 90, or a nucleic acid molecule having an identity of at least85% to the nucleic acid molecule comprising a nucleotide sequence selected from the group ofSEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 90, or anucleic acid molecule which is homologous to the the nucleic acid molecule comprising anucleotide sequence selected from the group of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 90, wherein the homology is at least 85%.Embodiment 227. The C5a binding agent for use of any one of Embodiments 203, 204, 205206, 210, 212, 213, 214 and 215, wherein the nucleic acid molecule comprises a nucleotidesequence selected from the group of SEQ ID NO: 14, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 37, SEQ ID NO: 57, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 91 and SEQ ID NO: 92, or a nucleic acid molecule havingan identity of at least 85% to the nucleic acid molecule comprising a nucleotide sequence selected from the group of 14, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 37, SEQ ID NO: 57, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 91 and SEQ ID NO: 92, or a nucleic acid molecule which is homologous to the thenucleic acid molecule comprising a nucleotide sequence selected from the group of 14, SEQ IDNO: 21, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 37, SEQ ID NO: 57, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 91 and SEQ ID NO: 92, wherein the homology is at least 85%.Embodiment 228. The C5a binding agent for use of any one of Embodiments 203, 204, 205,206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226 and 227, wherein the nucleic acid molecule is capable of binding human C5a and mouse C5a.Embodiment 229. The C5a binding agent for use of any one of Embodiments 203, 204, 205,206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227 and 228, wherein the nucleic acid molecule comprises at least one binding moiety which is capable of binding human C5a and mouse C5a, wherein such binding moiety consists of L-nucleotides.Embodiment 230. The C5a binding agent for use of any one of Embodiments 203, 204, 205,206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224,225, 226, 227, 228 and 229, wherein the nucleotides of or the nucleotides forming the nucleic acid molecule are L-nucleotides.Embodiment 231. The C5a binding agent for use of any one of Embodiments 134, 135, 136,137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155,156, 157, 158, 159, 160 and 161, wherein the nucleic acid molecule is an L-nucleic acid molecule.Embodiment 232. The C5a binding agent for use of any one of Embodiments 203, 204, 205,206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230 and 231, wherein the nucleic acid is an antagonist of an activity mediated by human and / or mouse C5a.Embodiment 233. The C5a binding agent for use of any one of Embodiments 203, 204, 205,206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224,225, 226, 227, 228, 229, 230, 231 and 232, wherein the nucleic acid molecule comprises amodification group, wherein excretion rate of the nucleic acid molecule comprising themodification group from an organism is decreased compared to a nucleic acid not comprisingthe modification group.Embodiment 234. The C5a binding agent for use of any one of Embodiments 203, 204, 205,206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231 and 232, wherein the nucleic acid molecule comprises a modification group, wherein the nucleic acid molecule comprising the modification group has an increased retention time in an organism compared to a nucleic acid molecule not comprising the modification group.Embodiment 235. The C5a binding agent for use of any one of Embodiments 233 and 234,wherein the modification group is selected from the group comprising biodegradable and non- biodegradable modifications, preferably the modification group is selected from the group comprising polyethylene glycol, linear polyethylene glycol, branched polyethylene glycol, hydroxyethyl starch, a peptide, a protein, a polysaccharide, a sterol, polyoxypropylene, polyoxyamidate and poly (2-hydroxyethyl)–L-glutamine.Embodiment 236. The C5a binding agent for use of Embodiment 235, wherein themodification group is a polyethylene glycol, preferably consisting of a linear polyethylene glycol or branched polyethylene glycol, wherein the molecular weight of the polyethylene glycol is preferably from about 20,000 to about 120,000 Da, more preferably from about 30,000 to about 80,000 Da and most preferably about 40,000 Da.Embodiment 237. The C5a binding agent for use of Embodiment 235, wherein themodification group is hydroxyethyl starch, wherein preferably the molecular weight of the hydroxyethyl starch is from about 50 to about 1000 kDa, more preferably from about 100 to about 700 kDa and most preferably from 200 to 500 kDa.Embodiment 238. The C5a binding agent for use of any one of Embodiments 233, 234, 235,236 and 237, whereby the modification group is coupled to the nucleic acid molecule via alinker, whereby preferably the linker is a biodegradable linker.Embodiment 239. The C5a binding agent for use of any one of Embodiments 164, 165, 166,167, 168 and 169, wherein the modification group is coupled to the 5’-terminal nucleotideand / or the 3’-terminal nucleotide of the nucleic acid molecule.Embodiment 240. The C5a binding agent for use of any one of Embodiments 233, 234, 235,236, 237, 238 and 239, wherein the organism is an animal or a human body, preferably a humanbody.Embodiment 241. The C5a binding agent for use of any one of Embodiments203, 204, 205,206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239 and 240, wherein the is nucleic acid molecule comprises a nucleotide sequence of SEQ ID NO: 59 or of a SEQ ID NO: 92 and a modification, wherein the modification has modification group that is a polyethylene glycol, preferably consisting of a branched polyethylene glycol, wherein the molecular weight of the polyethylene glycol is about 40,000 Da.Embodiment 242. The C5a binding agent for use of Embodiment 241, wherein the nucleicacid molecule of a SEQ ID NO: 92 consists of phosphodiester-linked 37 L-RNA nucleotidesand 3 L-DNA nucleotides that is

[0003] conjugated at its 5’-end covalently to a hexylamino linker and 40 kDa PEG and the chemical name Embodiment 243. The C5a binding agent for use of any one of Embodiments 203, 204, 205,206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224,225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 and 242wherein the C5a binding agent is compound AON-D21.Embodiment 244. The C5a binding agent for use of Embodiment 243, whereinAON-D21 is represented by the following structural formula:

[0004] (structural formula I) wherein NHC6H12O is a hexylamino linker and R is and n is approximately 450, wherein the molecular formula is C398H458N160Na40O287P40[C2H4O]2n, wherein n is approximately 450.Embodiment 245. The C5a binding agent for use of Embodiment 246, wherein R is a PEG moiety with a molecular weight of about 40 kDa,the oligonucleotide part of AON-D21 as an anhydrous free acid is represented by structuralformula I without R (the PEG moiety), andthe molecular weight of the oligonucleotide part of AON-D21 as an anhydrous free acid is13167 Da.Embodiment 246. The C5a binding agent for use of any one of Embodiments 244 and 245,wherein AON-D21 comprises a nucleic acid moiety and a non-nucleic acid moiety, wherein the non-nucleic acid moiety is the PEG moiety preferably comprising the linker, and the nucleic acid moiety is the oligonucleotide part of AON-D21, preferably is the oligonucleotide part of AON-D21 as an anhydrous free acid.Embodiment 247. The C5a binding agent for use of any one of Embodiments 244, 245 and246, wherein0.2 mg of AON-D21 per kg body weight of the subject corresponds to 15.19 nmol of AON-D21 per kg body weight of the subject.Embodiment 248. The C5a binding agent for use of Embodiment 247, wherein the 0.2 mgof AON-D21 refers to the oligonucleotide part of AON-D21as an anhydrous, free acid.Embodiment 249. The C5a binding agent for use of any one of Embodiments 243, 244,245, 246, 247 and 248, whereinthe method comprises administering to the subject a dose of 0.2 mg of AON-D21 per kg bodyweight of the subject or a dose of 15.19 nmol of AON-D21 per kg body weight of the subjectevery 11 to 13 hours, preferably every 12 hours, wherein the route of administration is an intravenous infusion, wherein the intravenousinfusion is a central intravenous infusion or intravenous peripheral infusion,wherein the duration of the infusion is 15 to 30 minutes.The present inventors have found that a dosage regimen for a C5a binding agent that leads to alevel of the C5a binding agent in the blood of a subject that is lower than a typically observedlevel of C5 in blood of a subject of about 450 nM, allows an inhibition of 100 % of an activityof C5a contained in blood of the subject. This finding is surprising because the level of C5a inblood of a subject, even in a subject suffering from a disease that is associated with or caused by C5a, is significantly lower, typically by at least one magnitude, than the level of C5 in blood of such subject. This surprising finding has also been observed for a C5a binding agent that is capable of binding to both C5a and C5, and even further been observed for a C5a binding agent the binding affinity of which to both C5a and C5 is about the same.Furthermore, the present inventors have surprisingly found that a dosing and, respectively, adosage regimen according to the present invention reduces an activity of C5a in blood of asubject only for a period of time which is sufficiently long for achieving a desired therapeutic effect, but avoids or reduces treatment-emergent adverse events. Typically, a treatment- emergent adverse event results from suppressing the positive effect of C5a for too long after achieving the desired therapeutic effect upon which the treatment is usually terminated. In case of an anti-C5a therapy such as administering a C5a binding agent to a subject, a treatment-emergent adverse event may be an infection, typically a microbial infection arising frommicrobial invasion due to a missing C5a-mediated pro-inflammatory response of the subject’s immune system. According to the present invention as disclosed herein and subject to the different aspects including any embodiment thereof, and if not explicitly indicated to the contrary, the C5a binding agent is or is to be administered such that the C5a binding agent is administered to the subject at a point in time when the C5a binding agent is present in the blood of the subject at a desired level, such as the trough level, or the C5a binding agent is or is to be administered such that the C5a binding agent is administered to the subject at a point in time when the C5a binding agent is assumed to be present in the blood of the subject at a desired level, such as the trough level. In a preferred embodiment of each and any aspect including any embodiment thereof the desired level of the C5a binding agent in blood of the subject is from about 80 nM to about 300 nM, preferably from about 80 nM to about 200 nM, more preferably from about 100 nM to about 150 nM and most preferably about 100 nM. It will be acknowledged by a person skilled in the art that, in an embodiment of each and any aspect, including any embodiment thereof, a level of the C5a binding agent assumed to be existing in a subject, preferably in blood of the subject, is a level which is one assumed by a person skilled in the art to exist, whereby preferably such assumption is based on earlier measurement(s) of the level of the C5a binding agent in the subject to which the C5a binding agent is or is to be administered or in a subject different therefrom. Preferably, such subject different therefrom is a subject suffering from or being at risk of suffering from the same or a similar disease than the subject to which the C5a binding is or is to be administered. More preferably, such assumed level is determined based on pharmacokinetic and / or pharmacodynamic characteristics of the C5a binding agent to be administered to the subject. Determining such pharmacokinetic and pharmacodynamic characteristics is a matter of routine for a person skilled in the art.The problems underlying the present invention are solved in a first aspect by a C5a bindingagent for use in a method of treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering to the subject multiple doses of the C5a binding agent at a level of the C5a binding agent, preferably a troughlevel of the C5a binding agent, of 80 to 300 nM in the blood of the subject. In such method twoor more doses of the C5a binding agent are administered to the subject. A dose of the C5a binding agent is administered to the subject at a trough level which preferably means that the C5a binding agent is administered to the subject at a point in time when the level of the C5abinding agent in the subject is the same as or close to the trough level of the C5a binding agentin the subject. Determinig the level of the C5a binding agent in the subject is within the skills of a person of the art. In an embodiment, the level of the C5a binding agent in the subject isdetermined one or several times for determining whether the trough level has been reached. Itwill be appreciated by a person skilled in the art that based on considerations relying onpharmacokinetics and pharmacodynamics as well as empirical data, in particular empirical data of the individual subject, the reaching of the trough level can also be calculated and thus the administration of the next dose scheduled for a distinct point in time based on such calculation. Preferably, a level of the C5a binding agent in the subject is close to the trough level of the C5a binding agent in the subject if the administration of the next dose of the C5a binding agent to the subject is suitable to increase the level of the C5a binding agent in the subject such that the desired therapeutic effect which is intended to be achieved by such next dose of the C5a binding agent is achieved. The range of levels which are regarded as being close to the trough level areknown to a person skilled in the art such as a person managing the disease in the subject or maybe determined by routine methods. In an embodment, a level of the C5a binding agent is close to the trough level if said level of the C5a binding agent is ± 10 % of the trough level or less, preferably ± 5 % of the trough level or less and more prefebaly ± 3 % of the trough level or less. It will be appreciated by a person skilled in the art that there may be a gap between the point in time when the level of the C5a binding agent is determined in the subject and the administrationof any of the multiple doses of the C5a binding agent. Preferably, such gap in time does nothave any impact on the treating and / or preventing of the disease associated with or caused by C5a and the tolerable length of such gap is known to a person skilled in the art such as a personmanaging the disease in the subject. Preferably, such gap in time comprises about 15 minutesand any multiples thereof up to one, two, three or four hours, whereby such gap also dependeon the frequence with such any dose of the C5a binding agent is administered to the subject. According to the present invention, the trough level of the C5a binding agent is from about 80 to about 300 nM. In an embodiment, the trough level is selected from 80 nM, 90 nM, 100 nM,110 nM, 120 nM, 130 nM, 140 nM, 150 nM, 160 nM, 170 nM, 180 nM, 190 nM, 200 nM, 210nM, 220 nM, 230 nM, 240 nM, 250 nM, 260 nM, 270 nM, 280 nM, 290 nM, and 300 nM;preferably, the trough level is selected from 80 nM, 90 nM, 100 nM, 110 nM, 120 nM and 130nM; more preferably, the trough level is selected from 80 nM, 90 nM and 100 nM; most preferably the trough level is 100 nM. The problems underyling the present invention are solved in a second aspect by a C5a binding agent for use in a method of treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering to the subject multiple doses of the C5a binding agent at a level of the C5a binding agent in the blood of thesubject of 80 to 300 nM. The level of the C5a binding agent in the blood of the subject of 80 to300 nM may also be referred to as the minimum level.In such method two or more doses of the C5a binding agent are administered to the subject. A dose of the C5a binding agent is administered to the subject at a minimum level which preferably means that the C5a binding agent is administered to the subject at a point in timewhen the level of the C5a binding agent in the subject is the same as or close to the minimumlevel of the C5a binding agent in the subject. Determinig the level of the C5a binding agent in the subject is within the skills of a person of the art. In an embodiment, the level of the C5a binding agent in the subject is determined one or several times for determining whether the minimum level has been reached. It will be appreciated by a person skilled in the art that based on considerations relying on pharmacokinetics and pharmacodynamics as well as empirical data, in particular empirical data of the individual subject, the reaching of the minimum level can also be calculated and thus the administration of the next dose scheduled for a distinct point in time based on such calculation. Preferably, a level of the C5a binding agent in the subject is close to the minimum level of the C5a binding agent in the subject if the administration of the next dose of the C5a binding agent to the subject is suitable to increase the level of the C5a binding agent in the subject such that the desired therapeutic effect which is intended to be achieved by such next dose of the C5a binding agent is achieved. The range of levels which are regarded as being close to the minimum level are known to a person skilled in the art such as a person managing the disease in the subject or may be determined by routine methods. In an embodment, a level of the C5a binding agent is close to the minimum level if said level of the C5a binding agent is ± 10 % of the minimum level or less, preferably ± 5 % of the trough level or less and more prefebaly ± 3 % of the minimum level or less. It will be appreciated by a person skilled in the art that there may be a gap between the point in time when the level of the C5a binding agent is determined in the subject and the administration of any of the multiple doses of the C5a binding agent. Preferably, such gap in time does not have any impact on the treating and / or preventing of the disease associated with or caused by C5a and the tolerable length of such gap is known to a person skilled in the art such as a person managing the disease in the subject. Preferably, such gap in time comprises about 15 minutes and any multiples thereof up to one, two, three or four hours, whereby such gap also depends on the frequence with such any dose of the C5a binding agent is administered to the subject. According to the present invention, the trough level of the C5a binding agent is from about 80 to about 300 nM. In an embodiment, the trough level is selected from 80 nM, 90 nM, 100 nM,110 nM, 120 nM, 130 nM, 140 nM, 150 nM, 160 nM, 170 nM, 180 nM, 190 nM, 200 nM, 210nM, 220 nM, 230 nM, 240 nM, 250 nM, 260 nM, 270 nM, 280 nM, 290 nM, and 300 nM;preferably, the trough level is selected from 80 nM, 90 nM, 100 nM, 110 nM, 120 nM and 130nM; more preferably, the trough level is selected from 80 nM, 90 nM and 100 nM; most preferably the trough level is 100 nM.The problems underyling the present invention are solved in a third aspect by a C5a bindingagent for use in a method of treating and / or preventing a disease in a subject, wherein the diseaseis associated with or caused by C5a, wherein the method comprises administering to the subjectthe C5a binding agent during a treatment period, wherein the administering of the C5a bindingagent provides a level of the C5a binding agent in the blood of the subject, wherein the level ofthe C5a binding agent in the blood of the patient isa) a minimum level of 80 to 300 nM maintained during the treatment period of thesubject; orb) a minimum level of 80 to 300 nM at the end of the treatment period of the subject.According to this third aspect, the C5a binding agent is or is to be administered to a subject when the level of the C5a binding agent is the same as or close to a minimum level of the C5a binding, whereby such minimum level is from about 80 nM to about 300 nM. In an embodiment, the minimum level is maintained during the treatment period of the subject, i.e. during the period in time when the subject is treated. In an alternative embodiment, the minimum level is maintained at the end of a treatment period of the subject, i.e. at a point in time when the subject is is no longer treated of the treatment of the subject has been terminated. In such method two or more doses of the C5a binding agent are administered to the subject. A dose of the C5a binding agent is administered to the subject at a minimum level which preferably means that the C5a binding agent is administered to the subject at a point in timewhen the level of the C5a binding agent in the subject is the same as or close to the minimumlevel of the C5a binding agent in the subject. Determinig the level of the C5a binding agent in the subject is within the skills of a person of the art. In an embodiment, the level of the C5a binding agent in the subject is determined one or several times for determining whether the minimum level has been reached. It will be appreciated by a person skilled in the art that based on considerations relying on pharmacokinetics and pharmacodynamics as well as empirical data, in particular empirical data of the individual subject, the reaching of the minimum level can also be calculated and thus the administration of the next dose scheduled for a distinct point in time based on such calculation. Preferably, a level of the C5a binding agent in the subject is close to the minimum level of the C5a binding agent in the subject if the administration of the next dose of the C5a binding agent to the subject is suitable to increase the level of the C5a binding agent in the subject such that the desired therapeutic effect which is intended to be achieved by such next dose of the C5a binding agent is achieved. The range of levels which are regarded as being close to the minimum level are known to a person skilled in the art such as a person managing the disease in the subject or may be determined by routine methods. In an embodment, a level of the C5a binding agent is close to the minimum level if said level of the C5a binding agent is ± 10 % of the minimum level or less, preferably ± 5 % of the trough level or less and more prefebaly ± 3 % of the minimum level or less. It will be appreciated by a person skilled in the art that there may be a gap between the point in time when the level of the C5a binding agent is determined in the subject and the administration of any of the multiple doses of the C5a binding agent. Preferably, such gap in time does not have any impact on the treating and / or preventing of the disease associated with or caused by C5a and the tolerable length of such gap is known to a person skilled in the art such as a person managing the disease in the subject. Preferably, such gap in time comprises about 15 minutes and any multiples thereof up to one, two, three or four hours, whereby such gap also depends on the frequence with such any dose of the C5a binding agent is administered to the subject. According to the present invention, the trough level of the C5a binding agent is from about 80 to about 300 nM. In an embodiment, the trough level is selected from 80 nM, 90 nM, 100 nM,110 nM, 120 nM, 130 nM, 140 nM, 150 nM, 160 nM, 170 nM, 180 nM, 190 nM, 200 nM, 210nM, 220 nM, 230 nM, 240 nM, 250 nM, 260 nM, 270 nM, 280 nM, 290 nM, and 300 nM;preferably, the trough level is selected from 80 nM, 90 nM, 100 nM, 110 nM, 120 nM and 130nM; more preferably, the trough level is selected from 80 nM, 90 nM and 100 nM; most preferably the trough level is 100 nM. According to this third aspect, the method comprises administering to the subject the C5a binding agent during a treatment period, whereby such treatment comprises administering to the subject at last a first dose of the C5a binding agent and the administering to the subject at least a last dose of the C5a binding agent. In an embodiment, the treatment period starts withthe administering of the first dose of the C5a binding agent which is administered to the subjectand ends at a time at which the level of the C5a binding agent in the blood of the subject fallsbelow 80 to 300 nM or is lower than 80 to 300 nM after the last dose of the C5a binding agentwas administered. In an alternative embodiment, the treatment period starts with a first dose ofa C5a binding agent which is administered to the subject and ends when a medical practitioner terminates it or declares it to be terminated. Preferably the medical practitioner is a medical doctor, a nurse or a medical practitioner service provider. Alternatively or more preferably, the medical practitioner is a person who is in charge of managing the disease of the subject. Symptoms / side effects taking into consideration one or more characteristics of the subjectselected from the group comprising the overall health condition, age, gender, course of thedisease associated with or caused by C5a, other disease(s) from which the subject suffers or is at risk of suffering, prognosis of the disease associated with or caused by C5a, in particular taking into consideration genetic disposition and family history. In an embodiment of the third aspect which is also an embodiment of each and any embodiment of the third aspect, the treatment period’s beginning is defined by a first administration of theC5a binding agent followed. In connection therewith it will be appreciated by a person skilledin the art that the subject may be a naïve subject, i.e. a subject to which a and in particular the C5a binding agent has not been administered, at least not administered in the treatment of the same disease.The problems underyling the present invention are solved in a fourth aspect by a C5a bindingagent for use in a method for treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering theC5a binding agent to the subject, wherein an activity of C5a in the blood of the subject isreduced by 50% or less within 24 to 72 hours after administering the C5a binding agent to thesubject. According to this method an activity of C5a is reduced by 50 % or less which preferably means that an activity of C5a is back to at leat 50 % of its original activity in the blood of the subject within 24 to 72 hours. This preferably means that the activity of C5a is reduced by at least 50 % and any percentage lower than 50 % including but not limited to 45 %, 40 %, 35 %, 30 %, 25%, 20 %, 15 %, 10 %, 5 % and 0%. Recuding an activity of C5a by 0 % means that the activity of C5a is 100 %. In an embodimtent, the term within 24 to 72 hours means that as early as 24 hours and as late as 72 hours after administering the C5a binding agent to the subject, an activity of the C5a contained in the blood of the subject is reduced by 50 % or less, or inother words, an activity of C5a contained in the blood of a subject is at – again – least 50 % ormore, preferably at least 50 % or more of the activity prior to the administering of the C5a binding agent to the subject.The problems underyling the present invention are solved in a fifth aspect by a C5a bindingagent for use in a method for treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the treating and / or preventing comprises administering the C5a binding agent to the subject, wherein the treating and / or preventing of the disease is associated with or goes along with a reduced adverse effect or a reduced risk of an adverse effect, wherein the adverse effect is caused by or arising from the administering of the C5a binding agent, wherein an activity of C5a in the blood of the subject is reduced by 50 % or less within 24 hours to 72 hours after administering the C5a binding agent to the subject.According to this method an activity of C5a is reduced by 50 % or less which preferably meansthat an activity of C5a is back to at leat 50 % of its original activity in the blood of the subject within 24 to 72 hours. This preferably means that the activity of C5a is reduced by at least 50 % and any percentage lower than 50 % including but not limited to 45 %, 40 %, 35 %, 30 %, 25%, 20 %, 15 %, 10 %, 5 % and 0%. Recuding an activity of C5a by 0 % means that the activity of C5a is 100 %. In an embodimtent, the term within 24 to 72 hours means that as early as 24 hours and as late as 72 hours after administering the C5a binding agent to the subject, an activity of the C5a contained in the blood of the subject is reduced by 50 % or less, or in otherwords, an activity of C5a contained in the blood of a subject is at – again – least 50 % or more,preferably at least 50 % or more of the activity prior to the administering of the C5a binding agent to the subject.The problems underyling the present invention are solved in a sixth aspect by a C5a bindingagent for use in a method for treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the treating and / or preventing comprisesadministering the C5a binding agent to the subject, wherein the treating and / or preventing ofthe disease is associated with or goes along with a reduced adverse effect or a reduced risk of an adverse effect, wherein the adverse effect is caused by or arising from the administering of the C5a binding agent, wherein the C5a binding agent has plasma half-life of about 6 hours to about 15 hours within the first 12-48 hours after administering the C5a binding agent to the subject as determined in the blood of the subject.The problems underyling the present invention are solved in a seventh aspect by a C5a bindingagent for use in a method for reducing an adverse effect or for reducing the risk of an adverse effect of an anti-C5a therapy administered to a subject, wherein the method comprises administering to the subject a C5a binding agent, wherein an activity of C5a in the blood of the subject is reduced by 50 % or less within 24 hours to 72 hours after administering the C5abinding agent to the subject. According to this method an activity of C5a is reduced by 50 % orless which preferably means that an activity of C5a is back to at leat 50 % of its original activity in the blood of the subject within 24 to 72 hours. This preferably means that the activity of C5a is reduced by at least 50 % and any percentage lower than 50 % including but not limited to 45 %, 40 %, 35 %, 30 %, 25%, 20 %, 15 %, 10 %, 5 % and 0%. Recuding an activity of C5a by 0 % means that the activity of C5a is 100 %. In an embodimtent, the term within 24 to 72 hours means that as early as 24 hours and as late as 72 hours after administering the C5a binding agent to the subject, an activity of the C5a contained in the blood of the subject is reduced by 50 %or less, or in other words, an activity of C5a contained in the blood of a subject is at – again –least 50 % or more, preferably at least 50 % or more of the activity prior to the administering of the C5a binding agent to the subject. The problems underyling the present invention are solved in a eighth aspect by a C5a binding agent for use in a method for reducing an adverse effect or for reducing the risk of an adverse effect of an anti-C5a therapy administered to a subject, wherein the method comprises administering to the subject a C5a binding agent, wherein the C5a binding agent has a plasma half-life of about 6 hours to about 15 hours within the first 12-48 hours after administering the C5a binding agent to the subject hours as determined in the blood of the subject. In an embodiment of any one of the fouth, fifth, sixth, seventh and eighth aspect, including any embodiment thereof, at least a first and a least a second dose of the C5a binding agent are administered to the subject. In such embodiment the at least second dose is the last dose. If subsequent to the second dose subsequent doses are administered to the subject the last of such subsequent doses to be administered to the subject is the last dose administered.The problems underyling the present invention are solved in a ninth aspect by a C5a bindingagent for use in a method of treating and / or preventing a disease in a subject, wherein the disease is which is associated with or caused by C5a, wherein the method comprises administering to the subject a) a total amount of 4.18 to 222.25 nmol of the C5a binding agent per kg bodyweight ofthe subject over a period of 8 to 48 hours, or b) a total amount of 0.055 to 2.9 mg of the C5a binding agent per kg bodyweight of thesubject over a period of 8 to 48 hours.The problems underyling the present invention are solved in a tenth aspect by a C5a bindingagent for use in a method of treating and / or preventing a disease in a subject, wherein the disease is which is associated with or caused by C5a, wherein the method comprises administering tothe subject 15.19 nmol of AON-D21 per kg body weight of the subject every 11 to 13 hours,preferably every 12 hours. The problems underlying the present invention are solved in an eleventh aspect by a C5a binding agent for use in a method for treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering to the subject several individual doses Df of the C5a binding agent, wherein a dose Df of the several individual doses Df, preferably each of the several individual doses Df, is as follows:Df = Dose x (1 ± v), wherein (Formula I) wherein Df = dose to be administered (nmol / kg body weight of the subject),I = dosing interval (h),Ctrough = target level of the C5a binding agent in blood of the subject (nmol / L) at steadystate, 0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject. In an embodiment of the eleventh aspect, including any embodiment thereof and as preferably used herein, a target level is the lowest level to be realized in the blood of the subject upon administration of the C5a binding agent. In an embodiment of the eleventh aspect, including any embodiment thereof and as preferably used herein, a level of the C5a binding agent at steady state is a level of the C5a binding agent, preferably a trough level of the C5a binding agent, which is constant, at least about constant, between the various administrations of the C5a binding agent. In an embodiment of the eleventh aspect, including any embodiment thereof and as preferably used herein, a target level of the C5a binding agent is a desired level of the C5a binding agent or a level which, preferably for therapeutic reasons is to be realized in the subject. In a preferred embodiment of the eleventh aspect, including any embodiment thereof and as more preferably used herein, a target level of the C5a binding agent is a desired trough level of the C5a binding agent or a trough level which, preferably for therapeutic reasons is to be realized in the subject. In an embodiment of the eleventh aspect, including any embodimentthereof and as preferably used herein, the terms several individual doses and multiple doses areused interchangeably and synonymously if not explicitly indicated to the contrary. In a more preferred embodiment of the eleventh aspect, including any embodiment thereof, the several individual doses Df form a plurality of individual doses Df which are or are to be administered to the subject one after the after. In a preferred embodiment of the eleventh aspect, including any embodiment thereof, all of the individual doses Df are the same. In an alternative embodiment of the eleventh aspect, including any embodiment thereof, the individual doses Df are different. In an embodiment of the eleventh aspect, including any embodiment thereof, theinitial elimination half-life t1 / 2 is determined at a Cmax of the C5a binding agent. Methods fordetermining such Cmax are known to a person skilled in the art and, for example, also disclosed in Example 12.1.2 herein. In a preferred embodiment of the eleventh aspect, including any embodiment thereof, the Cmax of a C5a binding agent is a maximum observed level of the C5a binding agent in blood of the subject after the C5a binding agent has been administered to the subject, preferably has been administered to the subject several times. In an embodiment of the eleventh aspect, including any embodiment thereof, a or the dosing interval I, preferably with hours as dimension, is the time difference between two subsequent administrations of the C5a binding agent to the subject. In a more preferred embodiment of the eleventh aspect, including any embodiment thereof, the time difference between two subsequent administrations of the C5a binding agent is the time difference between to subsequent doses Df of the several individual doses Df. In a further preferred embodiment of the eleventh aspect, including any embodiment thereof, the dosing interval I is the same for all administrations of the several individual doses Df. In an alternative embodiment of the eleventh aspect including any embodiment thereof, the dosing interval I is different between the administrations of the several individual doses Df. In connewction with some embodiments of the eleventh aspect, the elimination half-life t1 / 2 was surpisingly found to be dependent on the Cmax was determined at a Cmax of the C5a binding agent from about 90 nmol / L to about 7300 nmol / L, preferably at a Cmax of the C5a binding agent from about 94 nmol / L to about 7280 nmol / L, more preferably at a Cmax of the C5a binding agent from about 94 nmol / L to about 5274 nmol / L. It will be appreciated by a person skilled in the art that by means of the C5a binding agent for use in a method for treating and / or preventing a disease in a subject as defined in the eleventh aspect, including any embodiment thereof, and such method, respectively, a dose of the C5a binding agent can be determined which is to be administered to the subject so as to reach or establish in the subject a previously defined level of the C5a binding agent at steady state,preferably a previously defined trough level of the C5a binding agent at steady state.The problems underlying the present invention are solved in a twelfth aspect by a C5a binding agent for use in a method for treating and / or preventing a disease in a subject, wherein thedisease is associated with or caused by C5a, wherein the method comprises administering tothe subject several individual doses Di of the C5a binding agent, wherein a dose Di of the several individual doses Di, preferably each of the several individual doses Di is as follows:Di = Dose x (1 ± v), wherein

[0005] (Formula II) wherein Di = dose to be administered (nmol / kg body weight of the subject),I = dosing interval (h),Ctrough = target level of the C5a binding agent in blood of the subject (nmol / L)after the first dose of the C5a binding agent has been administered to the subject, 0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject or wherein the method comprises administering to the subject only a single dose Ds, the single dose Ds is calculated as follows:Ds = Dose x (1 ± v), wherein^^^^ = ^0.0713 +∙ nmol⁄ ^ ^nmol⁄ L ^^ kg ∙ h ^ ∙ ^ (Formula III) whereinDs = single dose of the C5a binding agent to be administered (nmol / kg body weightof the subject),I = Interval from dosing for which inhibition of elevated C5a shall be present (h),Cmin = minimal concentration of the C5a binding agent in blood of the subject (nmol / L)required for inhibition at the Interval I after Ds has been administered to thesubject, 0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject. In an embodiment of the twelfth aspect, including any embodiment thereof, if only a single doseis to be administered to the subject, the dose is calculated as follows:Ds = Dose x (1 ± v), whereinnmol⁄ kg^^^^ = ^0.0713nmol⁄ L ∙ ^^^^ − 0.0156 nmol⁄ kg ^nmol⁄ kg ∙ h^+ ^0.0002nmol⁄ L ∙ ^^^^ + 0.0279 nmol⁄ kg ∙ h^ ^ ∙ ^^(Formula III)Ds = single dose of the C5a binding agent to be administered (nmol / kg body weightof the subject),I = Interval from dosing for which inhibition of elevated C5a shall be present (h),Cmin = minimal concentration of the C5a binding agent in blood of the subject (nmol / L)required for inhibition at the Interval I after Ds has been administered to thesubject, 0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject. In an embodiment of the twelfth aspect, including any embodiment thereof and as preferably used herein, a target level is the lowest level to be realized in the blood of the subject upon administration of the C5a binding agent. In an embodiment of the twelfth aspect, including any embodiment thereof and as preferably used herein, a target level of the C5a binding agent is a desired level of the C5a binding agent or a level which, preferably for therapeutic reasons, is to be realized in the subject. In a preferred embodiment of the twelfth aspect, including any embodiment thereof and as more preferably used herein, a target level of the C5a binding agent is a desired trough level of the C5a binding agent or a trough level which, preferably for therapeutic reasons is to be realized in the subject. In an embodiment of the twelfth aspect, including any embodiment thereof and as preferably used herein, the terms several individualdoses and multiple doses are used interchangeably and synonymously if not explicitly indicatedto the contrary. In a more preferred embodiment of the twelfth aspect, including any embodiment thereof, the several individual doses Di form a plurality of individual doses Di which are or are to be administered to the subject one after the after. In a preferred embodiment of the twelfth aspect, including any embodiment thereof, all of the individual doses Di are the same. In an alternative embodiment of the twelfth aspect, including any embodiment thereof,the individual doses Di are different. In an embodiment of the twelfth aspect, including anyembodiment thereof, the elimination half-life t1 / 2which is surprisingly dependent on the Cmax of the C5a binding agent, is determined at a Cmax of the C5a binding agent. Methods for determining such Cmax are known to a person skilled in the art and, for example, also disclosed in Example 12.1.2 herein. In a preferred embodiment of the twelfth aspect, including any embodiment thereof, Cmax of a C5a binding agent is a maximum observed level of the C5a binding agent in blood of the subject after the C5a binding agent has been administered to the subject, preferably has been administered to the subject several times. In an embodiment of the twelfth aspect, including any embodiment thereof, a or the dosing interval I, preferably with hours as dimension, is the time difference between two subsequent administrations of the C5a binding agent to the subject. In a more preferred embodiment of the twelfth aspect, including any embodiment thereof, the time difference between two subsequent administrations of the C5a binding agent is the time difference between to subsequent doses Di of the several individual doses Di. In a further preferred embodiment of the twelfth aspect, including any embodiment thereof, the dosing interval I is the same for all administrations of the several individual doses Di. In an alternative embodiment of the twelfth aspect including any embodiment thereof, the dosing interval I is different between the administrations of the several individual doses Di. It will be appreciated by a person skilled in the art that by means of the C5a binding agent for use in a method for treating and / or preventing a disease in a subject as defined in the twelfth aspect, including any embodiment thereof, and such method, respectively, a dose of the C5a binding agent can be determined which is to be administered to the subject so as to reach or establish in the subject a previously defined level of the C5a binding agent after a first dose of the C5a binding agent has been or was administered to the subject. The problems underlying the present invention are solved in a 13thaspect by a C5a binding agent for use in a method for treating and / or preventing a disease in a subject, wherein thedisease is associated with or caused by C5a, wherein the method comprises administering tothe subject several individual doses Di of the C5a binding agent, wherein a dose Di of the several individual doses Di, preferably each of the several individual doses Di is as follows:Di = Dose x (1 ± v), wherein (Formula II) wherein Di = dose to be administered (nmol / kg body weight of the subject),I = dosing interval (h),Ctrough = target level of the C5a binding agent in blood of the subject (nmol / L)after the first dose of the C5a binding agent has been administered to the subject, 0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject; and wherein the method comprises administering to the subject several individual doses Df of the C5a binding agent, wherein a dose Df of the several individual doses Df, preferably each of the several individual doses Df, is as follows:Df = Dose x (1 ± v), whereinnmol⁄ kg^^^^ = ^0.0305nmol⁄ L ∙ ^^^^^^^ − 0.324 nmol⁄ kg ^0.0277 nmol⁄ kg ∙ h^ ^ ∙ ^^ (Formula I) wherein Df = dose to be administered (nmol / kg body weight of the subject),I = dosing interval (h),Ctrough = target level of the C5a binding agent in blood of the subject (nmol / L) at steadystate,0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject. It will be appreciated that each and any embodiment of the eleventh aspect, including any embodiment thereof and each and any embodiment of the twelfth aspect, including any embodiment thereof, form or constitute an embodiment of the 13thaspect.The problems underlying the present invention are solved in a 14th aspect by a C5a bindingagent for use in a method for treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises, after administrationof a loading dose of the C5a binding agent to the subject, continuously administering the C5abinding agent to the subject, wherein a dose for continuous administration Dca isDca = DoseContInf x (1 ± v), wherein (Formula IV), whereinDoseContInf = Continuous infusion dose per hour (nmol / kg (body weight of the subject)∙h),Ctarget = target level of the C5a binding agent in blood of the subject (nmol / L) that is oris to be constant over the duration of the continuous administration, 0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject. In an embodiment of the 14thaspect, including any embodiment thereof, Ctargetis a or the target level of the C5a binding agent in blood of the subject (nmol / L). In an embodiment of the 14thaspect, including any embodiment thereof, such target level is a target level which factually is or is intended to be essentially constant for a certain period of time. Preferably, such certain period of time is the time over which the C5a binding agent is continuously administered to the subject or is to be administered to the subject, more preferably after the administration of the loading dose to the subject. It will be acknowledged by a person skilled in the art that DNCmax can be determined by routine measure and more specifically as disclosed in Examples 12 and 13.1 herein.The problem underlying the present invention is solved in a 15th aspect by a C5a binding agentfor use in a method of treating a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the subject is suffering from the disease, and wherein the subject has an elevated C5a activity in the blood, wherein the method comprises administering to the subject a dose of the C5a-binding agent, wherein the C5a binding agent administered to the subject inhibits the elevated C5a activity in the blood of the subject to a healthy-state level or below a healthy-state level or below the healthy-state level, wherein the inhibition of the elevated C5a activity is, after a last administration of the C5a binding agent to the subject, effective for 24 to 72 hours. In an embodiment of the 15thaspect, including any embodiment thereof, the C5a binding agent can be administered only once or several times to the subject. In case the C5a binding agent is administered to the subject only once, such only once administration of the C5a binding agent constitutes the last administration of the C5a binding agent. In case several subsequent doses of the C5a binding agent are administered to the subject, the last of the several subsequent dosesof the C5a binding agent constitutes the last administration of the C5a binding agent.In an embodiment of the 15thaspect, including any embodiment thereof, the level of C5a activity in a state of health is a level of C5a in blood of a subject ≤ 3 nM as described by Zeleket al. (supra). Zelek et al. (supra) equally describe an assay for determining the level of C5a inblood of a subject. In an embodiment of the 15thaspect, including any embodiment thereof, the level of C5a activity is determined by means of the assay described in Zelek et al. (supra). The problem underlying the present invention is solved in a 16thaspect by a C5a binding agent for use in a method for treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering the C5a binding agent to the subject, wherein the method reduces treatment-emergent adverse events (TEAEs) or reduces the risk of treatment-emergent adverse events (TEAEs), wherein the C5a bindingagent is AON-D21 comprises a nucleotide sequence according to SEQ ID NO: 92 and isrepresented by the following structural formula: (structural formula I) wherein NHC6H12O is a hexylamino linker and R is and n is approximately 450, wherein the molecular formula is C398H458N160Na40O287P40[C2H4O]2n, wherein n is approximately 450.The problem underlying the present invention is solved in a 17th aspect by a C5a binding agentfor use in a method for treating and / or preventing a disease in a subject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering the C5a binding agent to the subject, wherein the method reduces treatment-emergent adverse events (TEAEs) or reduces the risk of treatment-emergent adverse events (TEAEs), wherein the C5a bindingagent has an initial elimination half-life t1 / 2 within the first 12 to 48 hours after administrationto a subject of about 5 hours to 15 hours. In an embodiment of the 17th aspect, including anyembodiment thereof, the C5a binding agent is binding to C5a and such binding of the C5a binding agent to C5a does not interfere with C5 cleavage. In an embodiment of each and any aspect, including any embodiment thereof, the term that the C5a binding agent does not interfere with C5 cleavage means that the cleavage of C5 by C5 convertase is at least 80%, at least 90%or at least 95 % of the cleavage observed in the absence of the C5a binding agent. An assay fordetermining whether a C5a binding agent interferes with the cleavage of C5 is known in the art. In an embodiment of the 17thaspect, including any embodiment thereof, the target level of the C5a binding agent is a level of the C5a binding agent of at least 50 nM. In an alternative embodiment of the 17thaspect, including any embodiment thereof, the target level of the C5a binding agent is a level of the C5a binding agent of at least 10 nM. In an embodiment of the 17thaspect, including any embodiment thereof, TEAEs are TEAEs resulting from or being associated with the blocking or inhibition of C5a and C5a activity, respectively, by a C5a binding agent. According to the present invention, the half-life t1 / 2 of the C5a binding agent disclosed herein results in such reduced TEAEs and such reduced risk of TEAEs. In a preferred embodiment of the 17thaspect, the severity of the TEAEs and their symptoms, respectively, is reduced.It will be understood by a person skilled in the art that the 16th aspect, including any embodimentthereof, may constitute an embodiment of the 17thaspect, including any embodiment thereof. The problems underlying the present invention are solved in an 18thaspect by a packaging comprising a C5a binding agent, wherein the packaging comprises a pharmaceutical composition of the C5a binding agent and information on the use of the pharmaceutical composition, wherein the information comprises dosage or dose of the C5a binding agent, wherein the dosage or dose is as defined in any one of the fist aspects to the 14thaspect, including any embodiment thereof. In an embodiment of the 18thaspect, including any embodiment thereof, the pharmaceutical composition is present as a unit dose, whereby it is preferred that such unit dose is present in a concentrated form, for example as a stock solution, which may be diluted prior to the administration of the C5a binding agent to the subject. It is within the present invention that the methods subject to the purpose-limited embodiments and claims are each and individually additional aspects of the present invention. The embodiments of the aspects related to or covered by the purpose-limited embodiments and claims are also embodiments of the corresponding additional aspects. This applies in partciuarl to each and any one of the first, second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, eleventh, twelfth, 13thand 14thaspects. It is within the present invention that each and any embodiment of an aspect is equally an embodiment of each and any other aspect, including any embodiment of such each and any other aspect.The C5a binding agent as used in accordance with the present invention and in particular itsvarious aspects, including any embodiment thereof are C5a-neutralizing drugs, i.e. drugs that bind to C5a and therefore inhibit the interaction of C5a and at least one of its receptors (tworeceptors, C5aR1 and C5aR2, are known to date). It will be appreciated that for theneutralization of the biological action of C5a, complex formation of the drug and C5a is needed. The ratio of the complex formed relative to the concentrations of the two binding partners and the affinity between the drug (D) and the ligand C5a (L) is calculated by the law of mass action as follows: The affinity as expressed by the equilibrium dissociation constant Kd is a measure for thestrength of the binding interaction with [D], [L] and [DL] being the molar concentrations drug, ligand and drug-ligand complex respectively: Therefore:[^^] =[^] ^⋅ [^]^For [D] = 10x Kd, the equation can be simplified to:[^^] = 10 ⋅[L]In words: 90% of the ligand (here C5a) are bound by the drug if the drug concentration is 10x higher than the Kd. Accordingly, if [D] = 100 x Kd,[^^] = 100 ⋅[L]In other words: 99% of the ligand (here C5a) are bound by the drug if the drug concentration is 100x higher than the Kd. If at least 90% inhibition is desired, which I find plausible, [D] should be 10x the Kd. So our general dosing regimen may be extended to drugs that have affinities 10 x smaller than our intended trough levels, i.e. Kd ≤ 8 nM, ≤ 9 nM, ≤ 10 nM, ≤ 20 nM or ≤ 30 nM for target (trough)levels of 80 nM, 90 nM 100 nM, 200 nM or 300 nM respectively, just to give some numericalexamples. It will be appreciated by a person skilled in the art that further dosage regimes may be used in the practicing of the present invention as disclosed herein. Such further dosage regimens includebut are not limited to those disclosed in Examples 13 and 14 which are incorporated into thisgeneral part of the description by reference. It will be further appreciated that the dosage regimens disclosed in Example 13 and 14 can be applied to any C5a binding agent, preferably a C5a binding agent having binding characteristics similar to compound AON-D21. Preferably, such binding characteristics consisit of binding to both C5a and C5 expressed by an affinity ofabout 0.1 to 5 nM, preferably 0.1 to 2 nM, more preferably 0.1 to 1.0 nM. for C5a and C5a andof one molecule of the C5a binding agent binding to one molecule of C5a and C5, respectively. In an embodiment of each and any aspect and as preferably used herein, a trough level or troughconcentration (Ctrough) is the concentration or level reached by a drug such as a C5a bindingagent, immediately before the next dose is administered. The name comes from the idea that ona graph of concentration versus time, the line forms a U-shaped trough at the lowest region,before a new dose sends it higher again. It will be appreciated by a person skilled in the art thatthe concept of a trough level is preferably applicable to a dosage regimen where multiple dosesare administered to a subject. Upon administration of the first dose of such dosage regimencomprising multiple doses to be administered to a subject, the level of the administered drugwill typically be lower than the intended level. After administration of more of the multipledoses a steady state will be achieved. It is preferred that the level achieved after the administration of more of the multiple doses is the trough level which triggers the administration of any subsequent dose to the subject and, respectively, the subsequent administration of a doses to the subject. In an embodiment, the first dose with which the drug is adminsterd to the subject is higher so as to make sure that such steady state of the drug in the subject is established faster. In an embodiment of each and any aspect of the invention, including any embodiment thereof, and as preferably used herein, administering to a or the subject multiple doses of the C5abinding agent means that at least a first dose of the C5a binding agent and at least a second doseof the C5a binding agent are administered to a or the subject, whereby the at least second dose of the C5a binding agent is administered subsequent to the at least first dose of the C5a binding agent. In this embodiment, the at least second dose of the C5a binding agent may also be referred to as the subsequent or the next dose of the C5a binding agent. In a preferred embodiment of each and any aspect of the invention, including any embodiment thereof, and as preferably used herein, administering to a or the subject multiple doses of the C5a binding agent means that at least a first dose of the C5a binding agent, at least a second dose of the C5a binding agent and at least one subsequent dose of the C5a binding agent are administered to a or the subject, whereby the at least second dose of the C5a binding agent is administered to a or the subject subsequent to the at least first dose of the C5a binding agent,and the at least one subsequent dose of the C5a binding agent is administered to a or the subjectsubsequent to the at least second dose of the C5a binding agent. In this embodiment, the at least second dose of the C5a binding agent and the at last one subsequent dose of the C5a binding agent may each also be referred to as next dose of the C5a binding agent. In a more preferred embodiment of each and any aspect of the invention, including any embodiment thereof, and as preferably used herein, administering to a or the subject multiple doses of the C5a binding agent means that at least a first dose of the C5a binding agent, at least a second dose of the C5a binding agent and more subsequent doses of the C5a binding agent are administered to a or the subject, whereby the at least second dose of the C5a binding agent is administered to a or the subject subsequent to the at least first dose of the C5a binding agent, a first of the more subsequent doses of the C5a binding agent is administered to a or the subject subsequent to the at least second dose of the C5a binding agent and a second of the more subsequent doses of the C5a binding agent is administered to a or the subject subsequent to the first of the more subsequent doses of the C5a binding agent etc. Depending on the number of the more subsequent doses the above outlined sequence of administering the individual doses of the more doses is continued accordingly. In an alternative embodiment of each and any aspect of the invention and as preferably usedherein, administering to the subject multiple doses of the C5a binding agent at a level of theC5a binding agent, such as a trough level, means that one of the multiple doses of the C5a binding agent is administered to the subject at distinct points in time in the method of treating or preventing a disease or a method for reducing an adverse effect or for reducing the risk of an adverse effect of an anti-C5a therapy administered to a subject, whereby such distinct points in time are defined by a level of the C5a binding agent in the blood of the subject, whereby such level is the indicated level, for example 80 to 300 nM. More preferably, at a single point in time only one of the multiple doses is administered to the subject. In an exemplary embodiment where the multiple doses comprises at first dose of the C5a binding agent, a second dose of the C5a binding agent and a third dose of the C5a binding agent, the first dose of the multiple doses of the C5a binding agent is administered to the subject at a first point in time in the method of treating and / or preventing a disease or in the method for reducing an adverse effect or for reducing the risk of an adverse effect of an anti-C5a therapy administered to a subject when the level of the C5a binding agent in the blood of the subject is a level of 80 to 300 nM. the second dose of the C5a binding agent is administered to the subject at a second point in time in the method of treating and / or preventing a disease or in the method for reducing an adverseeffect or for reducing the risk of an adverse effect of an anti-C5a therapy administered to asubject when, after the administration of the first dose of the C5a binding agent, the level of theC5a binding agent in the blood of the subject is – again - a level of 80 to 300 nM, and the third dose of the C5a binding agent is administered to the subject at third point in time in the method of treating and / or preventing a disease or in the method for reducing an adverse effect or for reducing the risk of an adverse effect of an anti-C5a therapy administered to a subject when, after administration of the second dose of the C5a binding agent, the level of the C5a bindingagent in the blood of the subject is - again - a level of 80 to 300 nMIn an embodiment of each and any aspect of the invention, including any embodiment thereof, and as preferably used herein, an activity of C5a is an activity of C5a as determined in a cell- based assay, wherein the cell-based assay makes use of a reporter cell line expressing a C5a receptor, whereby the reporter cell line generates a bioluminescent signal proportional to C5a and the level of C5a, respectively. An example of such a cell-based assay and a protocol for its use are described in Examples 12.1.3 and 8, whereby such cell-based assay and protocol are incorporated into this general part of the description by reference. In an alternative embodiment of each and any aspect of the invention, including any embodiment thereof, and as preferably used herein, an activity of C5a is selected from group comprising activity as a chemoattractant for inflammatory cells including leukocytes, activity stimulating respiratory burst, a cytokine and chemokine release activity and an activity for increasing vascular permeability. Methods and assays for determining such activity are known to a person skilled in the art. In an embodiment of each and any aspect of the invention, including any embodiment thereof, activity of C5a is directly linked to the concentration of C5a. This means that in such embodiment, any inhibition of the activity of C5a in a subject or a sample from such subject goes along with or is caused by a reduction in the level of C5a in the subject or in the sample from the subject. More preferably the concentration of C5a is the concentration of active C5a, whereby more preferably the concentration of active C5a is determined by tests and methods known in the art; such tests and method known in the art include the cell-based assay using a reporter cell line expressing C5a receptor is disclosed herein. In an embodiment of each and any aspect of the invention, including any embodiment thereof, an activity of the C5a is inhibited. The degree of such inhibition may range from 100 % to 0 %. Means and methods for determining such inhibition are known in the art and include, but are not limited to, the assay and test disclosed in Examples 8 and 12.1.3 of the instant application. In a more preferred embodiment, the activity of C5a is completely inhibited, i.e.100 % of theactivity of the C5a in blood of a subject is inhibited if the level of the C5a binding agent in theblood of the subject is 100 nM or higher. This applies in particular if the C5a binding agent is compound AON-D21. A person skilled in the art will acknowledge that the activity of the C5a in blood of a subject will also be completely inhibited, i.e.100 % of the activity of the C5a in blood of a subject is inhibited if the level of the C5a binding agent in the blood of the subject is higher than 100 nM, for example is 150 nM, 200 nM, 250 nM or 300 nM.It has been found that if, among others, the C5a antagonist is compound AON-D21, 80 % ofthe activity of C5a in blood of a subject is inhibited if the concentration of said C5a antagonist in the blood of the subject is about 80 nM. Similarly, it has been found that if, among others, the C5a antagonist is compound AON-D21, 90 % of the activity of C5a in blood of a subject is inhibited if the concentration of said C5a antagonist in the blood of the subject is about 90 nM. In an embodiment of each and any aspect of the invention, including any embodiment thereof, an adverse effect is reduced if the symptoms of or associated with such adverse effect are reduced. In an embodiment of each and any aspect of the invention, including any embodiment thereof, an adverse effect is avoided if the symptoms of or associated with such adverse effect are avoided. In an embodiment of each and any aspect of the invention, including any embodiment thereof, the risk for an adverse effect is reduced if the risks for symptoms or the risk of the subject to develop or show such symptoms of or associated with such adverse effect is reduced. In an embodiment of each and any aspect of the invention, including any embodiment thereof, therisk for an adverse effect is avoided if the risk for symptoms or the risk of the subject to developor show such symptoms of or associated with such adverse effect are avoided. In an embodiment of each and any aspect of the invention, including any embodiment thereof,the half-life of the C5a binding agent is determined. Such determining and methods fordetermining the half-life of a compound including of a C5a binding agent are known to a person skilled in the art In an embodiment thereof, the half-life is determined in the blood of the subject. In a preferred embodiment, the half-life of the C5a binding agent is about 15 hours or less, preferably about 6 hours to about 15 hours within the first 12 to 48 hours in the blood of the subject, more preferably the half-life of the C5a binding agent is about 15 hours or less within the first 12 to 48 hours in the blood of the subject after administering the C5a binding agent to the subject. In an embodiment of each and any aspect of the invention, including any embodiment thereof, any reference to a level of a C5a binding agent in the blood of a subject refers to a level of a C5a binding agent in a blood sample of the subject. In an embodiment of each and any aspect of the invention, including any embodiment thereof, any reference to an activity of C5a in the blood of a subject refers to an activity of C5a in a blood sample of the subject. In an embodiment of each and any aspect of the invention, including any embodiment thereof, any reference to a level of C5a in the blood of a subject refers to a level of C5a in a blood sample of the subject. In an embodiment of each and any aspect of the invention, including any embodiment thereof, an adverse effect of an anti-C5a therapy is an adverse effect caused by or associated with a C5a therapy, preferably the C5a therapy is administered to a subject which shows or is at risk of showing such adverse effect. More preferably such adverse effect is selected from the groupconsisting of lung edema, pneumonia, herpes simplex, Staphylococcus pneumonia and Herpessimplex reactivation. In a further embodiment the C5a therapy is a therapy comprising administering to a subject a C5a binding agent, including a C5a binding agent as disclosed herein. In an embodiment of each and any aspect of the invention, including any embodiment thereof,the term every two days means every 44 to 52, wherein more preferably every two days meansevery 46 to 50 hours, wherein most preferably every two days means every 48 hours.In an embodiment of each and any aspect of the invention, including any embodiment thereof,the term every day means every 20 to 28 hours, wherein preferably every day means every 22to 26 hours, wherein more preferably every day means every 23 to 25 hours, wherein most preferably every day means every 24 hours. In an embodiment of each and any aspect of the invention, including any embodiment thereof, the term twice day means every 10 to 14 hours, wherein preferably twice day means every 11 to 13 hours, wherein more preferably twice day means every 12 hours. In an embodiment of each and any aspect of the invention, including any embodiment thereof,the term three times a day means every 6 to 10 hours, wherein preferably three times day meansevery 8 hours. In an embodiment of each and any aspet of the present invention, including any embodiment thereof, the C5a binding agent is a C5a binding agent bibnding to C5a, whereby such binding to C5a does not interfere with C5 cleavage, in particular C5 cleavage by C5 convertase. More preferably such C5a binding agent is a C5a binding nucleic acid molecule. In an embodiment of each and any aspect of the present invention, including any embodiment thereof, the C5a binding agent is compound AON-D21 as defined herein., In an embodiment of each and any aspect of the present invention, including any embodiment thereof, AON-D21 is a covalent conjugate of a 40-mer L-oligonucleotide that terminates at the 5’-end in a hexylamino linker. A branched 40 kDa monomethoxy polyethylene glycol (PEG) unit is covalently attached to the amino linker via an N-alkyl amide linkage. AON-D21 at the intermediate stage, consisting of the pre-PEGylated oligonucleotide containing an amino- linker, is referenced hereinafter as AON-D21 prePEG. The chemical name for AON-D21 is:

[0006] AON-D21 is represented by the structural formula as shown in Figure 43.Molecular Formula: C398H458N160Na40O287P40[C2H4O]2n (where n is approximately 450) Molecular Weight AON-D21 prePEG free acid: 13,167 Da AON-D21 prePEG sodium salt: 14,047 Da AON-D21 free acid: 53,167 Da AON-D21 sodium salt: 54,047 Da Chirality / Stereochemistry AON-D21 has 157 chiral centers in the ribose backbone of the oligonucleotide. It is a single diastereomer with the all (L) configuration. The molecular weight allows the conversion of molar amounts and molar concentrations into weight and weight-based concentrations respectively.m = mass (g)n = molar amount (mol)M = molecular weight (g / mol)M (AON-D21) = 13167 g / mol as detailed above.And n = m / Mm = n ^ MConcentrations can be either molar concentrations Cmolar = n / V (mol / L) or weight-basedconcentrations Cweight-based = m / V (g / L).The conversion factor from weight-based concentrations in mg / L to molar concentrations innmol / L is the molar weight M as can be deduced from the above formulae, since the m in m / Vneeds to be converted to n or vice versa. For ease of use, the units are adjusted to10-6 mg / nmol. For AON-D21 this is: M = 13167 ^ 10-6 mg / nmolCmolar = n / V = (m / M) / V = (m / V) / M = Cweight-based / MFor AON-D21:Cmolar = Cweight-based / 13167^ 10-6 mg / nmol.Vice versa:Cweight-based = m / V = n^ M / V = n / V ^ M = Cmolar ^ MFor AON-D21: Conversion factors for AON-D21:1 mg / L / 13167 ^ 10-6 mg / nmol = 75.945 nmol / L1 nmol / L ^ 13167 ^ 10-6 mg / nmol = 0.013167 mg / LIn an embodiment of the present invention, including any embodiment thereof, the subject is a mammal, preferably a human being. It is, however, also within the present invention that such mammal is a mammal selected from the group comprising a monkey, an ape, a mouse, a rat, a dog, a cat, a horse, a cattle, a sheep, a goat and a pig. It will be acknowledged that any embodiment disclosed herein is an embodiment of each and any aspect of the present invention. Furthermore, any embodiment of a particular aspect of the present invention is also an embodiment of each and any other aspects of the present invention, including any embodiment thereof. The terms “of the present invention”, “of the invention”,“according to the present invention” and “according to the invention” are used interchangeablyherein and refer to each and any aspect of such invention disclosed herein. The terms “level”, “concentration” and “titer” are used synonymously herein.The terms “subject” and “individual” are used synonymously herein.The terms “subject”, “individual” and “patient” are used synonymously herein, unless indicatedotherwise or differently. It will be acknowledged that any reference to kg is actually a reference to kg body weight of a subject unless explicitly indicated to the contrary. According to the present invention the C5a binding agent is capable of binding to C5a and / or C5, preferably capable of binding to C5a and C5.In an embodiment of invention, the C5a binding agent is an agent having a binding affinity toC5a with a KD of about 0.1 to 5 nM, preferably 0.1 to 2 nM, more preferably 0.1 to 1.0 nM.In an embodiment the C5a binding agent is an inhibitor of an activity mediated by human C5a,wherein preferably the inhibitor is an antagonist. In a preferred embodiment is the C5a bindingagent an inhibitor of an activity mediated by human C5 having an inhibitory constant IC50 of about 0.1 to 5 nM, preferably 0.1 to 2 nM, more preferably 0.1 to 0.5 nM. In another preferredembodiment is the C5a binding agent capable of inhibiting C5a activity in the presence of C5.In a preferred embodiment the binding affinity of the C5a binding agent to C5 and C5a is below 10nM, more preferably below 10 nM and most preferably below 1 nM. In another preferred embodiment the dosing regime leads to plasma concentrations of the C5a binding agent of more than 100 nM. It will be appreciated by a person skilled in the art that the terms elimination half-life t1 / 2 and plasma half-life are used interchangeably and synonymously herein if not explicitly indicated to the contrary. It will be appreciated by a person skilled in the art that the terms blood and plasma are used interchangeably and synonymously herein if not explicitly indicated to the contrary. It will be appreciated by a person skilled in the art that the terms healthy state and state of health are used interchangeably and synonymously herein if not explicitly indicated to the contrary.In a preferred embodiment the C5a binding agent is an antibody or antigen-binding fragmentthereof, a peptide, an anticalin protein or a nucleic acid molecule, wherein the nucleic acidmolecule is preferably an L-aptamer (also referred to as spiegelmer, Spieglemer, L-aptamer orL-Aptamer).The term "antibody" typically refers to a glycoprotein comprising at least two heavy (H) chainsand two light (L) chains inter-connected by disulfide bonds, or an antigen-binding portion thereof. The term "antibody" also includes all recombinant forms of antibodies, e.g. antibodies expressed in prokaryotes, unglycosylated antibodies, and any antigen-binding antibody fragments and derivatives as described below. Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as VH or VH) and a heavy chain constant region. Each light chain is comprised of a light chain variable region (abbreviated herein as VL or VL) and a light chain constant region. The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant regions of the antibodies may mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (Clq) of the classical complement system. The term "antigen-binding fragment" of an antibody (or simply "binding portion"), as used herein, refers to one or more fragments of an antibody that retain the ability to specifically bind to an antigen. It has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody. Examples of binding fragments encompassed within the term "antigen-binding portion" of an antibody include (i) Fab fragments, monovalent fragments consisting of the VL, VH, CL and CH domains; (ii) F(ab')2 fragments, bivalent fragments comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) Fd fragments consisting of the VH and CH domains; (iv) Fv fragments consisting of the VL and VH domains of a single arm of an antibody, (v) dAb fragments, which consist of a VH domain; (vi) isolated complementarity determining regions (CDR), and (vii) combinations of two or more isolated CDRs which may optionally be joined by a synthetic linker. Furthermore, although the two domains of the Fv fragment, VL and VH, are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single chain Fv (scFv);). Such single chain antibodies are also intended to be encompassed within the term "antigen-binding fragment" of an antibody. A further example is a binding-domain immunoglobulin fusion protein comprising (i) a binding domainpolypeptide that is fused to an immunoglobulin hinge region polypeptide, (ii) animmunoglobulin heavy chain CH2 constant region fused to the hinge region, and (iii) an immunoglobulin heavy chain CH3 constant region fused to the CH2 constant region. Thebinding domain polypeptide can be a heavy chain variable region or a light chain variableregion. The binding-domain immunoglobulin fusion proteins are further disclosed in US 2003 / 0118592 and US 2003 / 0133939. These antibody fragments are obtained using conventional techniques known to those with skill in the art, and the fragments are screened forutility in the same manner as are intact antibodies. Further examples of "antigen- bindingfragments" are so-called microantibodies, which are derived from single CDRs.Thus, the term "antibody or antigen-binding fragment thereof,” as used herein, refers toimmunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e. molecules that contain an antigen-binding site that immunospecifically binds an antigen. The term "peptide" typically refers to any polymer of (same or different) amino acids joined via peptide bonds. The term "anticalin proteins" typically refers to artificial proteins that are able to bind to antigens, either to proteins or to small molecules. They are not structurally related to antibodies, which makes them a type of antibody mimetic. Instead, they are derived from human lipocalins which are a family of naturally binding proteins. Anticalin proteins are being used in lieu of monoclonal antibodies, but are about eight times smaller with a size of about 180 amino acids and a mass of about 20 kDa. The term "dosage regimen" (also referred to as “dosage regime”, “dosing regime”, “dosing regimen”, “dose regimen”, “dose regime”) ntypically refers to a schedule of doses of a medicine, including the time between doses, the duration of treatment and the amount to be taken each time. Dosage regimens also include how a medicine is to be taken, and in what formulation (dosage form). The nucleic acid molecule according to the present invention binds specifically and with highaffinity to both mouse C5a and human C5a, thereby inhibiting the binding of C5a to its C5areceptor, although the sequence homology of mouse C5a and human C5a is only 64 % in thehomologous region and mouse C5a having 3 additional N-terminal amino acids. Moreover, in contrast to human C5a, mouse C5a is not glycosylated. Asparagine64, the glycosylation site in human C5a is mutated to glutamate in mouse. It is within the present invention that the nucleic acid according to the present invention is anucleic acid molecule. Insofar the terms nucleic acid and nucleic acid molecule are used hereinin a synonymous manner if not indicated to the contrary. Moreover, such nucleic acid(s) is / are preferably also referred to herein as the nucleic acid molecule(s) according to the (present) invention, the nucleic acid(s) according to the present invention, the inventive nucleic acid(s) or the inventive nucleic acid molecule(s).The features of the nucleic acids according to the present invention as described herein can berealised in any aspect of the present invention where the nucleic acid is used, either alone or in any combination. As to the various diseases, conditions and disorders which may be treated or prevented by usingthe C5a binding agent in a dosage regimen according to the present invention and compositions,preferably pharmaceutical compositions comprising the same, it has to be acknowledged that such diseases, conditions and disorders are those which are described herein, including and in particular those described and set forth in the introductory part of the instant application. Insofar, the respective passages of the specification and the introductory part of the specificationform an integral part of the present disclosure teaching the suitability of the dosage regimenusing a C5a binding agent of the present invention for the prevention and treatment,respectively, for said diseases, conditions, and disorders. Additionally, the dosage regimen using a C5a binding agent according to the present invention is preferred if the physiologicaleffect of the C5a – C5a receptor axis is related to higher plasma levels of C5a.As used herein the term C5a refers to any C5a including, but not limited to, mammalian C5a.Preferably, the mammalian C5a is selected from the group comprising human, rat, mouse,monkey C5a (see C5a species alignment in Fig. 11). More preferably the C5a is human C5a.Human C5a is a basic protein having the amino acid sequence according to SEQ. ID. No.50.Mouse C5a is a basic protein having the amino acid sequence according to SEQ. ID. No. 52.As outlined in more detail in the claims and example 1, the present inventors could moresurprisingly identify a number of different binding nucleic acid molecules capable of bindingboth human and mouse C5a. As outlined in more detail herein, the present inventors have identified a number of different C5a binding nucleic acid molecules capable of binding both, human and mouse C5a, wherebythe nucleic acid molecules can be characterised in terms of stretches of nucleotides which arealso referred to herein as disclosed (see Example 1). As experimentally shown in examples theinventors could surprisingly demonstrate in several systems that the nucleic acid molecule according to the present invention issuitbale for the treatment of a disease. Each of the different types of C5a binding nucleic acid molecules of the invention that bind toC5a comprises three different stretches of nucleotides: a first terminal stretch of nucleotides, acentral stretch of nucleotides and a second terminal stretch of nucleotides. In general, C5abinding nucleic acid molecules of the present invention comprise at their 5’-end and the 3’-endeach one of the terminal stretches of nucleotides, i.e. the first terminal stretch of nucleotides or the second terminal stretch of nucleotides (also referred to as 5’-terminal stretch of nucleotides and 3’-terminal stretch of nucleotides). The first terminal stretch of nucleotides and the second terminal stretch of nucleotides can, in principle due to their base complementarity, hybridize to each other, whereby upon hybridization a double-stranded structure is formed. However, such hybridization is not necessarily realized in the molecule under physiological and / or non-physiological conditions. The three stretches of nucleotides of C5a binding nucleic acidmolecules - the first terminal stretch of nucleotides, the central stretch of nucleotides and secondterminal stretch of nucleotides - are arranged to each other in 5’ ^ 3’-direction: the firstterminal stretch of nucleotides – the central stretch of nucleotides – the second terminal stretch of nucleotides. Alternatively, the second terminal stretch of nucleotides, the central stretch ofnucleotides and the terminal first stretch of nucleotides are arranged to each other in 5’ ^ 3’-direction. The length of the central stretch of nucleotides of the nucleic acids according to the present invention is preferably 34. The length of the first terminal stretch of nucleotides of the nucleic acids according to thepresent invention is between one and five nucleotides, preferably between three and fivenucleotides, more preferably three nucleotides.The length of the second terminal stretch of nucleotides of the nucleic according to the presentinvention is between one and five nucleotides, preferably between three and five nucleotides,more preferably three nucleotides.The terms ‘stretch’ and ‘stretch of nucleotides’ are used herein in a synonymous manner if not indicated to the contrary.The differences in the sequences of the defined stretches between the different C5a bindingnucleic acid molecules may influence the binding affinity to C5a. Based on binding analysis ofthe different C5a binding nucleic acid molecules of the present invention the central stretch andthe nucleotides forming the same are individually and more preferably in their entirety essentialfor binding of the C5a binding nucleic acid molecule to C5a.In a preferred embodiment the nucleic acid molecule according to the present invention is a single nucleic acid molecule. In a further embodiment, the single nucleic acid molecule is present as a multitude of the single nucleic acid molecule or as a multitude of the single nucleic acid molecule species. It will be acknowledged by the ones skilled in the art that the nucleic acid molecule in accordance with the invention preferably consists of nucleotides which are covalently linked to each other, preferably through phosphodiester links or linkages. It is within the present invention that the nucleic acid molecule according to the presentinvention comprises two or more stretches or part(s) thereof that can, in principle, hybridisewith each other. Upon such hybridisation a double-stranded structure is formed. It will be acknowledged by the ones skilled in the art that such hybridisation may or may not occur,particularly under in vitro and / or in vivo conditions. Also, in case of hybridisation, suchhybridisation does not necessarily occur over the entire length of the two stretches where, at least based on the rules for base pairing, such hybridisation and thus formation of a double- stranded structure may, in principle, occur. As preferably used herein, a double-stranded structure is a part of a nucleic acid molecule or a structure formed by two or more separate strands or two spatially separated stretches of a single strand of a nucleic acid molecule, whereby at least one, preferably two or more base pairs exist which are base pairing preferably in accordance with the Watson-Crick base pairing rules. It will also be acknowledged by the one skilled in the art that other base pairing such as Hoogsten base pairing may exist in or may form such double-stranded structure. It is also to be acknowledged that the feature that two stretches hybridize preferably indicates that such hybridization is assumed to happen due to base complementarity of the two stretches regardless of whether such hybridization actuallyoccurs in vivo and / or in vitro. In connection with the present invention such stretches are thefirst terminal stretch of nucleotides and the second stretch of nucleotides which, in an embodiment, may hybridize as defined above. In a preferred embodiment the term arrangement as used herein, means the order or sequence of structural or functional features or elements described herein in connection with the nucleic acids molecule(s) disclosed herein.It will be acknowledged by the person skilled in the art that the C5a binding agent is capable ofbinding to C5a or to both C5a and C5. It will be acknowledged by the person skilled in the artthat the a nucleic acid according to the present invention, is capable of binding to both C5a andC5. This binding characteristic arises from the fact that for the identification of the nucleic acids a moiety of C5a was used which is present in both C5a and C5. Also, it will be acknowledgedby the person skilled in the art that the nucleic acid molecule according to the present inventionis an antagonist to both C5 and C5a. Because of this the nucleic acids according to the presentinvention are suitable for the treatment and prevention, respecticely, of any disease which is associated with or caused by either C5a or C5 or both. The scientific rational may be taken from the prior art which establishes that C5a and C5, respectively, are involved or associated with a variety of diseases and conditions, respectively, and which is incoroporated herein by reference.The C5a binding nucleic acid molecule of present invention disclosed herein have been shownto recognize C5a in the context of C5 (see Example 1). Therefore, it was investigated whetherC5 cleavage to the anaphylatoxin C5a and C5b, which is part of the membrane attack complex (MAC) is inhibited by C5a binding nucleic acids. The MAC is the ultimate product of the complement cascade: a pore consisting of C5b-9. MAC is believed to insert into the cytoplasmic membranes of pathogens and kill them by induction of cytoplasmic leakage. The assay for C5cleavage was achieved by using a complement-dependent sheep erythrocyte hemolysis test. TheC5a binding molecule of the invention did not inhibit hemolysis (see Example 6). The C5abinding nucleic acid molecule of the invention does not interfere with C5 cleavage and MACformation and are therefore selective antagonists of C5a only. If used as a medicament, thismay be advantageous in many diseases, since the formation of the MAC that is beneficial inpathogen defense is not compromised in their presence.The nucleic acid molecule according to the present invention shall also comprise nucleic acidswhich are essentially homologous to the particular sequences disclosed herein. The termsubstantially homologous shall be understood such as the homology is at least 75%, preferably 85%, more preferably 90% and most preferably more that 95 %, 96 %, 97 %, 98 % or 99%. The actual percentage of homologous nucleotides present in the nucleic acid according to the present invention will depend on the total number of nucleotides present in the nucleic acid. The percent modification can be based upon the total number of nucleotides present in the nucleic acid. The homology between two nucleic acid molecules can be determined as known to the person skilled in the art. More specifically, a sequence comparison algorithm may be used for calculating the percent sequence homology for the test sequence(s) relative to the reference sequence, based on the designated program parameters. The test sequence is preferably the sequence or nucleic acid molecule which is said to be homologous or to be tested whether it ishomologous, and if so, to what extent, to a different nucleic acid molecule, whereby suchdifferent nucleic acid molecule is also referred to as the reference sequence. In an embodiment,the reference sequence is a nucleic acid molecule as described herein, preferably a nucleic acidmolecule having a sequence according to any one of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 90, SEQ ID NO: 14, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 37, SEQ ID NO: 57, SEQ IDNO: 59, SEQ ID NO: 60, SEQ ID NO: 91 and SEQ ID NO: 92. Optimal alignment of sequencesfor comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman (Smith & Waterman, 1981) by the homology alignment algorithm of Needleman & Wunsch (Needleman & Wunsch, 1970) by the search for similarity method of Pearson & Lipman (Pearson & Lipman, 1988), by computerized implementations of these algorithms (GAP,BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, GeneticsComputer Group, 575 Science Dr., Madison, Wis.), or by visual inspection. One example of an algorithm that is suitable for determining percent sequence identity is the algorithm used in the basic local alignment search tool (hereinafter "BLAST "), see, e.g. Altschul et al (Altschul et al.1990 and Altschul et al, 1997). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (hereinafter "NCBI"). The default parameters used in determining sequence identity using the software available from NCBI, e.g., BLASTN (for nucleotide sequences) and BLASTP (for amino acid sequences) are described in McGinnis et al (McGinnis et al , 2004).The nucleic acids according to the present invention shall also comprise nucleic acids whichhave a certain degree of identity relative to the nucleic acids disclosed herein and defined by their nucleotide sequence. More preferably, the instant invention also comprises those nucleic acid molecules which have an identity of at least 75%, preferably 85%, more preferably 90% and most preferably more than 95 %, 96 %, 97 %, 98 % or 99% relative to the nucleic acids disclosed herein and defined by their nucleotide sequence or a part thereof. The term inventive nucleic acid or nucleic acid according to the present invention shall also comprise those nucleic acids comprising the nucleic acids sequences disclosed herein or part thereof, preferably to the extent that the nucleic acids or said parts are involved in the binding to human C5a. Such nucleic acid is, in an embodiment, one of the nucleic acid molecules described herein, or a derivative and / or a metabolite thereof, whereby such derivative and / or metabolite are preferably a truncated nucleic acid compared to the nucleic acid molecules described herein. Truncation may be related to either or both of the ends of the nucleic acids as disclosed herein. Also, truncation may be related to the inner sequence of nucleotides of thenucleic acid, i.e. it may be related to the nucleotide(s) between the 5’ and the 3’ terminalnucleotide, respectively. Moreover, truncation shall comprise the deletion of as little as a single nucleotide from the sequence of the nucleic acids disclosed herein. Truncation may also berelated to more than one stretch of the inventive nucleic acid(s), whereby the stretch can be aslittle as one nucleotide long. The binding of a nucleic acid according to the present invention can be determined by the ones skilled in the art using routine experiments or by using or adopting a method as described herein, preferably as described herein in the example part. The nucleic acid molecule according to the present invention may be either a D-nucleic acid molecule or an L-nucleic acid molecule. Preferably, the nucleic acid molecule according to the present invention is an L-nucleic acid molecule. More preferably, the nucleic acid molecule ofthe present invention is a Spiegelmer or L-aptamer.It is also within the present invention that, in an embodiment, each and any of the nucleic acid molecules described herein in their entirety in terms of their nucleic acid sequence(s) are limited to the particular indicated nucleotide sequence(s). In other words, the terms “comprising” or “comprise(s)” shall be interpreted in such embodiment in the meaning of containing or consisting of. An L-nucleic acid as used herein is a nucleic acid or nucleic acid molecule consisting of L- nucleotides. A D-nucleic acid as used herein is nucleic acid or nucleic aicd molecule consisting of D- nucleotides. The terms nucleic acid and nucleic acid molecule are used herein in an interchangeable manner if not explicitly indicated to the contrary.Also, if not indicated to the contrary, any nucleotide sequence is set forth herein in 5’ 3’direction. As preferably used herein any position of a nucleotide is determined or referred to relative to the 5’ end of a sequence, a stretch or a substretch containing such nucleotide. Accordingly, a second nucleotide is the second nucleotide counted from the 5’ end of the sequence, stretch and substretch, respectively. Also, in accordance therewith, a penultimate nucleotide is the seond nucleotide counted from the 3’ end of a sequence, stretch and substretch, respectively. Irrespective of whether the nucleic acid molecule of the invention consists of D-nucleotides, L- nucleotides or a combination of both with the combination being e.g. a random combination or a defined sequence of stretches consisting of at least one L-nucleotide and at least one D-nucleic acid, the nucleic acid may consist of desoxyribonucleotide(s), ribonucleotide(s) or combinations thereof. It is also within the present invention that the nucleic acid molecule consists of both ribonucleotides and 2’deoxyribonucleotides. The 2´deoxyribonucleotides and ribonucleotidesare shown in Fig. 20 and 21. In order to distinguish between ribonucleotides and2’deoxyribonucleotides in the sequences of the nucleic acid molecules according to the presentinvention the following reference code is used herein. The nucleic acid molecule according to the present invention consists of 2’deoxyribonucleotides, wherein dG is 2’deoxy-guanosine-5’-monophosphate, dC is 2’deoxy-cytidine-5’-monophosphate, dA is 2’deoxy-adenosine-5’-monophosphate, dU is 2’deoxy-uridine 5’monophosphate The nucleic acid molecule according to the present invention consists of ribonucleotides, wherein G is guanosine-5’-monophosphate, C is cytidine 5’-monophosphate, A is adenosine-5’-monophosphate, U is uridine-5’monophosphate. For definition of ribonucleotide sequence motifs, the IUPAC abbreviations for ambiguous nucleotides are used:S strong G or C;W weak A or U;R purine G or A;Y pyrimidine C or U;K keto G or U;M imino A or C;B not A C or U or G;D not C A or G or U;H not G A or C or U;V not U A or C or G;N all A or G or C or UDesigning the nucleic acid molecule of the invention as an L-nucleic acid molecule is advantageous for several reasons. L-nucleic acid molecules are enantiomers of naturallyoccurring nucleic acids. D-nucleic acid molecules, however, are not very stable in aqueoussolutions and particularly in biological systems or biological samples due to the widespread presence of nucleases. Naturally occurring nucleases, particularly nucleases from animal cells are not capable of degrading L-nucleic acids. Because of this, the biological half-life of an L- nucleic acid molecule is significantly increased in such a system, including the animal and human body. Due to the lacking degradability of L-nucleic acid molecules no nuclease degradation products are generated and thus no side effects arising therefrom observed in such a system including the animal and human body. This aspect distinguishes L-nucleic acid moelcules from factually all other compounds which are used in the therapy of diseases and / ordisorders involving the presence of C5. An L-nucleic acid molecule which specifically binds toa target molecule through a mechanism different from Watson Crick base pairing, or an aptamerwhich consists partially or completely of L-nucleotides, particularly with those parts of theaptamer being involved in the binding of the aptamer to the target molecule, is also called aSpiegelmer or L-aptamer. Aptamers and Spiegelmers or L-aptamers as such are known to aperson skilled in the art and are, among others, described in ‘The Aptamer Handbook’ (eds. Klussmann, 2006). It is also within the present invention that the nucleic acid molecule of the invention, regardless whether it is are present as a D-nucleic acid, L-nucleic acid or D,L-nucleic acid or whether it is DNA or RNA, may be present as single stranded or double stranded nucleic acid molecule. Typically, the nucleic acid molecule is a single stranded nucleic acid molecule which exhibits a defined secondary structure due to its primary sequence and may thus also form a tertiary structure. The nucleic acid molecule, however, may also be double stranded in the meaning that two strands which are complementary or partially complementary to each other are hybridised to each other. A possibility to determine the binding constants of the C5a binding agent, preferably the nucleicacid molecules according to the present invention, is the use of the plasmon resonance plasmonresonance spectroscopy as described in example 4 which confirms the above finding that thenucleic acids according to the present invention exhibit a favourable KD value range. An appropriate measure in order to express the intensity of the binding between the individual nucleic acid molecule and the target which is in the present case C5a is the so-called KDvalue which as such as well the method for its determination are known to the one skilled in the art. Preferably, the KDvalue of the C5a binding agent, preferably of the nucleic acids according tothe present invention, is below 10 nM. The above-mentioned KD of about 10 nM is a preferredupper limit for the KD value for a C5a binding agent in dosage regimen for the treatment of adisease. The lower limit for the KD of a C5a binding agent, preferably a target binding nucleic acid, can be as little as about 10 picomolar or can be higher. It is within the present inventionthat the KD values of C5a binding agent, preferably an individual nucleic acid of the nucleicacids of the present invention, binding to C5a is preferably within this range. Preferred ranges can be defined by choosing any first number within this range and any second number withinthis range. Preferred upper KD values are 10 nM and 1 nM, preferred lower KD values are 100pM and 10 pM. The more preferred upper KD value is 1 nM, the more preferred lower KD value is 100 pM.In addition to the binding properties of the C5a binding agent; preferably a nucleic acidmolecule according to the present invention, the C5a binding agent, preferably a nucleic acidmolecule according to the present inventions inhibits the function of the respective targetmolecule which is in the present case C5a. The inhibition of the function of C5a - for instancethe stimulation of the respective receptors as described previously - is achieved by binding ofthe C5a binding agent, preferably a nucleic acid molecule according to the present invention,to C5a and forming a complex of a C5a binding agent, preferably a nucleic acid moleculeaccording to the present invention, and C5a. Such complex of a C5a binding agent, preferablya nucleic acid molecule, and C5a cannot stimulate the receptors that normally are stimulated byC5a, i.e. C5a which is not present in a complex with a C5a binding agent, preferably a nucleicacid molecule of the invention. Accordingly, the inhibition of receptor function by a C5abinding agent, preferably a nucleic acid molecule according to the present invention, isindependent from the respective receptor that can be stimulated by C5a but results from preventing the stimulation of the receptor by C5a by the C5a binding agent, preferably the nucleic acid molecule according to the present invention.A possibility to determine the inhibitory constant of a C5a binding agent, preferably a nucleicacid molecule according to the present invention, is the use of the methods as described inexample 5 which confirms the above finding that the C5a binding agent, preferably the nucleicacids according to the present invention, exhibits a favourable inhibitory constant which allowsthe use of said C5a binding agent, preferably the nucleic acid, in a therapeutic treatmentscheme, preferably the dosage regimen according to the present invention. An appropriatemeasure in order to express the intensity of the inhibitory effect of the individual C5a bindingagent, preferably a nucleic acid molecule, on interaction of the target which is in the presentcase C5a and the respective receptor, is the so-called half maximal inhibitory concentration (abbr. IC50) which as such as well the method for its determination are known to the one skilled in the art. Preferably, the IC50 value shown by a C5a binding agent, preferably a nucleic acid moleculeaccording to the present invention, is below 1 µM. An IC50 value of about 1 µM is said to becharacteristic for a non-specific inhibition of target functions by a C5a binding agent, preferablya nucleic acid molecule. As will be acknowledged by the ones skilled in the art, the IC50 valueof a group of C5a binding agents such as the nucleic acid molecules according to the presentinvention is within a certain range. The above-mentioned IC50of about 1 µM is a preferredupper limit for the IC50 value. The lower limit for the IC50 of a C5a binding agent, preferably anucleic acid molecule, can be as little as about 10 picomolar or can be higher. It is within thepresent invention that the IC50 values of individual C5a binding agent, preferably a nucleic acid,binding to C5a is preferably within this range. Preferred ranges can be defined by choosing anyfirst number within this range and any second number within this range. Preferred upper IC50values are 10 nM and 1 nM, preferred lower IC50 values are 100 pM and 10 pM. The morepreferred upper IC50 value is 1 nM, the more preferred lower IC50 value is 100 pM.The nucleic acid molecules according to the present invention may have any length provided that they are still able to bind to the target molecule. It will be acknowledged in the art that there are preferred lengths of the nucleic acids according to the present inventions. Typically, the length is between 15 and 120 nucleotides. It will be acknowledged by the ones skilled in the art that any integer between 15 and 120 is a possible length for the nucleic acids according to the present invention. More preferred ranges for the length of the nucleic acids according to the present invention are lengths of about 20 to 100 nucleotides, about 20 to 80 nucleotides, about20 to 60 nucleotides, about 38 to 44 nucleotides and about 40 nucleotides.It is within the present invention that the C5a binding agent, preferably the nucleic acidmolecule of the present invention, comprises a moiety which preferably is a high molecularweight moiety and / or which preferably allows to modify the characteristics of the C5a binding agent, preferably the nucleic acid molecule in terms of, among others, residence time in theanimal body, preferably the human body. A particularly preferred embodiment of suchmodification is PEGylation and HESylation of the C5a binding agent, preferably the nucleicacids according to the present invention. As used herein PEG stands for poly(ethylene glycole) and HES for hydroxyethly starch. PEGylation as preferably used herein is the modification ofa C5a binding agent, preferably an nucleic acid molecule according to the present invention,whereby such modification consists of a PEG moiety which is attached to an C5a binding agent,preferably a nucleic acid molecule according to the present invention. HESylation as preferablyused herein is the modification of a C5a binding agent, preferably a nucleic acid moleculeaccording to the present invention, whereby such modification consists of a HES moiety whichis attached to a C5a binding agent, preferably a nucleic acid molecule according to the presentinvention. These modifications as well as the process of modifying a C5a binding agent,preferably a nucleic acid molecule using such modifications, is described in European patentapplication EP 1306382, the disclosure of which is herewith incorporated in its entirety by reference.In the case of PEG being such high molecular weight moiety the molecular weight is preferablyabout 20,000 to about 120,000 Da, more preferably from about 30,000 to about 80,000 Da and most preferably about 40,000 Da. In the case of HES being such high molecular weight moiety the molecular weight is preferably from about 50 kDa to about 1000 kDa, more preferably fromabout 100 kDa to about 700 kDa and most preferably from 200 kDa to 500 kDa. HES exhibitsa molar substitution of 0.1 to 1.5, more preferably of 1 to 1.5 and exhibits a substitution gradeexpressed as the C2 / C6 ratio of approximately 0.1 to 15, preferably of approximately 3 to 10.The process of HES modification is, e.g., described in German patent application DE 12004 006249.8 the disclosure of which is herewith incorporated in its entirety by reference.The modification can, in principle, be made to an C5a binding agent at any position thereof. In case of a nucleic acid molecule of the present invention preferably such modification is made either to the 5’ –terminal nucleotide, the 3’-terminal nucleotide and / or any nucleotide between the 5’ nucleotide and the 3’ nucleotide of the nucleic acid molecule. The modification and preferably the PEG and / or HES moiety can be attached to the C5a bindingagent, preferably the nucleic acid molecule of the present invention, either directly or indirectly,preferably indirectly through a linker. It is also within the present invention that the a C5abinding agent, preferably the nucleic acid molecule according to the present invention,comprises one or more modifications, preferably one or more PEG and / or HES moiety. In an embodiment the individual linker molecule attaches more than one PEG moiety or HES moietyto a C5a binding agent, preferably a nucleic acid molecule according to the present invention.The linker used in connection with the present invention can itself be either linear or branched. This kind of linkers are known to the ones skilled in the art and are further described in international patent applications WO2005 / 074993 and WO2003 / 035665. In a preferred embodiment the linker is a biodegradable linker. The biodegradable linker allowsto modify the characteristics of the C5a binding agent, preferably the nucleic acid moleculeaccording to the present invention, in terms of, among other, residence time in an animal body,preferably in a human body, due to release of the modification from a C5a binding agent,preferably a nucleic acid molecule according to the present invention. Usage of a biodegradablelinker may allow a better control of the residence time of a C5a binding agent, preferably anucleic acid molecule according to the present invention. A preferred embodiment of such biodegradable linker is a biodegradable linker as described in, but not limited to, international patent applications WO2006 / 052790, WO2008 / 034122, WO2004 / 092191 and WO2005 / 099768. It is within the present invention that the modification or modification group is a biodegradablemodification, whereby the biodegradable modification can be attached to the C5a bindingagent, preferably the nucleic acid molecule of the present invention, either directly or indirectly,preferably through a linker. The biodegradable modification allows modifying thecharacteristics of the C5a binding agent, preferably the nucleic acid molecule according to thepresent invention, in terms of, among other, residence time in an animal body, preferably in ahuman body, due to release or degradation of the modification from the C5a binding agent,preferably the nucleic acid molecule according to the present invention. Usage of abiodegradable modification may allow a better control of the residence time of the C5a bindingagent, preferably the nucleic acid molecule according to the present invention. A preferredembodiment of such biodegradable modification is biodegradable as described in, but not restricted to, international patent applications WO2002 / 065963, WO2003 / 070823, WO2004 / 113394 and WO2000 / 41647, preferably in WO2000 / 41647, page 18, line 4 to 24. Beside the modifications as described above, other modifications can be used to modify thecharacteristics of the C5a binding agent, preferably the nucleic acid molecule according to thepresent invention, whereby such other modifications may be selected from the group ofproteins, lipids such as cholesterol and sugar chains such as amylase, dextran etc..Without wishing to be bound by any theory, by modifying a C5a binding agent, preferably thenucleic acid molecule according to the present invention, with a high molecular weight moietysuch as a polymer and more particularly one or several of the polymers disclosed herein, which are preferably physiologically acceptable, the excretion kinetic of the thus a C5a binding agent,preferably the modified nucleic acid molecule of the invention from an animal or human bodyto which the modified a C5a binding agent, preferably the nucleic acid molecule of theinvention, is administered is changed is changed. More particularly, due to the increasedmolecular weight of the thus modified a C5a binding agent, preferably the nucleic acid moleculeof the invention, excretion from an animal body, preferably from a mammalian body and morepreferably from a human body is decreased. As excretion typically occurs via the kidneys, the present inventors assume that the glomerular filtration rate of the thus modified the C5a bindingagent, preferably the nucleic acid molecule, is significantly reduced compared to a C5a bindingagent, preferably a nucleic acid molecule, not having this kind of high molecular weightmodification which results in an increase in the residence time of the C5a binding agent,preferably the modified nucleic acid molecule, in the animal body. In connection therewith it isparticularly noteworthy that, despite such high molecular weight modification the specificity ofthe C5a binding agent, preferably the nucleic acid molecule according to the present inventionis not affected in a detrimental manner. In an embodiment of each and any aspect, including any embodiment thereof, a preferred C5a binding agent is the C5a binding nucleic acid molecule AON-D21 which is also referred to as NOX-D21 herein and which is disclosed, among others, in WO 2013 / 104540.However, it is also within the present invention that the C5a binding agent, preferably thenucleic acid molecule according to the present invention, does not comprise any modificationand particularly no high molecular weight modification such as PEG or HES.The inventive C5a binding agent, preferably the nucleic acids according to the presentinvention, and / or the antagonists according to the present invention may be used for the generation or manufacture of a medicament. Such medicament or a pharmaceutical composition according to the present invention contains at least one of the inventive C5a binding agent,preferably the nucleic acids, optionally together with further pharmaceutically activecompounds, whereby the inventive C5a binding agent, preferably the nucleic acid, preferablyacts as pharmaceutically active compound itself. Such medicaments comprise in preferred embodiments at least a pharmaceutically acceptable carrier. Such carrier may be, e.g., water, buffer, PBS, glucose solution, preferably a 5% glucose salt balanced solution, starch, sugar, gelatine or any other acceptable carrier substance. Such carriers are generally known to the oneskilled in the art. It will be acknowledged by the person skilled in the art that any embodiments,use and aspects of or related to the medicament of the present invention is also applicable to the pharmaceutical composition of the present invention and vice versa. The indication, diseases and disorders for the treatment and / or prevention of which the C5abinding agent, preferably the nucleic acid, the pharmaceutical compositions and medicamentsin accordance with or prepared in accordance with the present invention result from the involvement, either direct or indirect, of C5a in the respective pathogenetic mechanism. The local release of C5a at sites of inflammation results in powerful pro-inflammatory stimuli. Thus, neutralization of C5a might be beneficial in many acute or chronic conditions, such as immune complex associated diseases in general (Heller et al., 1999); neurodegeneration and inflammation, e.g. in Alzheimer’s disease (Bonifati & Kishore, 2007), where the complement C5a receptor antagonist PMX205 improved behavioral parameters and a reduction ofpathological markers such as fibrillar deposits and activated glia (Fonseca et al. 2009). Otherinflammatory diseases with C5a involvement are systemic lupus erythematosus (Jacob et al.2010a; Jacob et al. 2010b), asthma (Kohl, 2001); secondary damages of trauma (Yao et al.1998); septic shock (Huber-Lang et al., 2001); systemic inflammtory response syndrome (SIRS); multiorgan failure (MOF); acute respiratory distress syndrome (ARDS); inflammatory bowel syndrome (IBD) (Woodruff et al., 2003); immune-complex-mediated renal disease (Wang, 2006), e.g. as a complication of systemic lupus erythematosus (Manderson et al, 2004); infections and their consequences (e.g. vascular leakage or bone loss such as bone losssecondary to periodontitis (Breivik et al.2011)); severe burns (Piccolo et al., 1999); reperfusioninjury of organs such as heart, spleen, bladder, pancreas, stomach, lung, liver, kidney, limbs,brain, sceletal muscle or intestine (Riley et al., 2000; Gueler et al. 2008; Khan et al. 2011; vander Pals et al. 2010; Zheng et al. 2008) that may lead amongst others to delayed graft function(Lewis et al, 2008) or fibrosis and / or remodelling of the organ, e.g. after an infarction of heart, brain or lung leading to secondary damage; psoriasis (Bergh et al., 1993); myocarditis; multiple sclerosis (Muller-Ladner et al., 1996); paroxysmal nocturnal hemoglobinuria (PNH), hemolysis, thromboembolism (Hill et al.2017) and rheumatoid arthritis (RA) (Woodruff et al., 2002; Hornum et al., 2017; Köhl 2019), resection of renal cell carcinoma and activation of osteoclasts promoting bone destruction, e.g. resulting in osteoarthtitis or delayed healing. Complement C5a has also been found in elevated amounts in drusen in age-related macular degeneration and it has been shown to lead to increased VEGF-expression and to promote choroidal neovascularization that may lead to vision impairment and loss (Nozaki et al, 2006). The complement system is part of the body’s innate defence system against infections. Invading pathogen trigger a proteolytic cascade that results in the tagging and elimination of the microbial intruders and orchestrates immunological and inflammatory processes [Ricklin, D., et al., 2010]. Important terminal effector mechanisms are mediated by complement C5 cleavage products C5a and C5b. C5b has a direct anti-bacterial function by initiating the formation of the terminal complement complex (TCC; also known as membrane attack complex, MAC), a pore-forming multi-protein complex (C5b-9) that results in the lysis of bacteria (mainly gram- negative). C5a has no direct anti-microbial effect but acts as an amplifier of numerous inflammatory processes including neutrophil activation (production of pro-inflammatory cytokines, NETosis), vascular activation and coagulation (Figure 2). In pneumonia, these processes are critical for disease progression to severe hyper-inflammatory states with lung failure and septic complications involving immunothrombosis and disseminated intravascular coagulation (DIC), extrapulmonary organ damage and shock [Bosmann, M., et al., 2013; Finsterbusch, M., et al., 2014; Laudes, I.J., et al., 2002; Chauhan, A.J., et al., 2020; Skendros, P., et al., 2020; Guo, R.F. and P.A. Ward, 2005]. Preclinical lung infection models (bacterial and viral) in rodent and non-rodent species have shown that inhibition of C5a can reduce local and systemic inflammatory responses and attenuates damage of the lung and extrapulmonary organs [Jiang, Y., et al., 2018; Sun, S., et al., 2015; Sun, S., et al., 2013; Song, N., et al., 2018; Muller-Redetzky, H., 2020]. Clinical data supports a role of C5a in lung infectious diseases. C5a levels are increased in patients with severe pneumonia [Muller-Redetzky, H., 2020; Carvelli, J., 2020; Cugno, M., et al., 2020; Gao, T., et al., 2020]. In a Phase 3 clinical trial, enrolling 369 invasive mechanically ventilated COVID-19 patients, C5a-blockade reduced the all-cause mortality rate at 28 days from 42%(95% CI 35 - 49) in the placebo group to 32% (95% CI 25–39) in treated group (hazard ratio0.67, 95% CI 0.48 - 0.96; p=0.027 using a predefined Cox regression model without site-stratification) [Vlaar, A.P.J., et al., 2022]. Activation of the complement system has also been shown to raise susceptibility to develop cerebral malaria in a mouse model. C5a or C5a receptor blockade using serum from mice immunized with theses molecules conferred resistance to cerebral malaria. Therefore, blocking the C5 C5a axis may be beneficial in the prevention of developing malaria, especially cerebralmalaria in humans (Patel et al. 2008).Autoimmune inflammatory diseases with complement involvement have been reviewedrecently (Chen et al. 2010). An expert review on possible and already pursued complement-targeted therapies appeared in Nature Biotechnology (Ricklin & Lambris, 2007). An updatewas published in Molecular Medicine in 2011 (Ehrnthaller et al. 2011).Of course, because the C5a binding agent, preferably aC5a binding nucleic acid according tothe present invention, interact with or bind to human C5a, a skilled person will generallyunderstand that the C5a binding agent, preferably a C5a binding nucleic acid according to thepresent invention can easily be used for the treatment, prevention and / or diagnosis of any disease of humans and animals as described herein. In connection therewith, it is to be acknowledged that the C5a binding agent, preferably a nucleic acid molecule according to the present invention can be used for the treatment and prevention of any of the diseases, disorder or condition described herein, irrespective of the mode of action underlying such disease, disorder and condition. In the following, and without wishing to be bound by any theory, the rational for the use of theC5a binding agent, preferably a nucleic acid molecule according to the present invention, inconnection with the various diseases, disorders and conditions is provided, thus rendering the claimed therapeutic, preventive and diagnostic applicability of the C5a binding agent,preferably a nucleic acid molecule according to the present invention, plausible. In order toavoid any unnecessary repetition, it should be acknowledged that due to the involvement of theC5a – C5a receptor axis as outlined in connection therewith said axis may be addressed by theC5a binding agent, preferably a nucleic acid molecule according to the present invention suchthat the claimed therapeutic, preventive and diagnostic effect is achieved. It should furthermore be acknowledged that the particularities of the diseases, disorders and conditions, of the patients and any detail of the treatment regimen described in connection therewith, may be subject to preferred embodiments of the instant application. Analyses of specimens from cancer patients indicate an activation of the complement system during cancer progression. Complement components are deposited on cancer cells and / orexpressed by cancer cells in tumors of lung (Corrales et al., 2012, Cho et al., 2014), ovary (Choet al., 2014), liver (Cho et al., 2014), kidney (Cho et al., 2014), endometrium (Cho et al., 2014), and thyroid gland (Lucas et al., 1996). Increased levels of complement activation marker C4d are found in bronchial fluids and plasma of lung cancer patients (Ajona et al., 2015). C3a and soluble C5b-9 are elevated in ovarian cancer ascites (Bjorge et al., 2005). Clinical data supports a potential tumor-promoting function of C5a showing that C5aR expression is associated with poor prognosis for patients with breast cancer (Imamura et al., 2016), gastric cancer (Kaida et al., 2016, Nitta et al., 2016), renal cell cancer (Xi et al., 2016), lung cancer (Gu et al., 2013), or ovarian cancer (Cho et al., 2014). C5a is released from humanlung cancer and colon cancer cell lines (Corrales et al., 2012, Piao et al., 2015). Increased C5ais found in the plasma of NSCLC patients (Corrales et al., 2012) and in human pancreatic neuroendocrine tumors (Contractor et al., 2016).The mechanisms underlying the tumor-promoting function of C5a are not fully understood anddifferent functions of C5a have been suggested including direct mitogenic effects (Cho et al., 2014), pro-angiogenic effects (Rutkowski et al., 2010, Nunez-Cruz et al., 2012), stimulation of cancer cell invasiveness (Nitta et al., 2013, Kaida et al., 2016), and the generation of an immunosuppressive tumor microenvironment to protect cancer cells from cellular immune surveillance in primary tumors (Markiewski et al., 2008, Corrales et al., 2012, Gunn et al., 2012, Sharma et al., 2015) or premetastatic sites and metastases (Vadrevu et al., 2014, Piao et al., 2015, Sharma et al., 2015, Contractor et al., 2016). The immunosuppressive function of C5a has been attributed to the recruitment and activation of C5aR1-expressing myeloid-derived suppressor (MDS) cells to the tumor, premetastatic siteand / or metastases. MDS cells were originally observed in cancer patient > 30 years ago, theirrole as spoilers of anti-tumor immunity is only now being appreciated. A heterogeneous population of normal myeloid cells trapped in intermediate stages of differentiation, MDS cells accumulate in the blood, lymph nodes and at tumor sites in virtually all cancer patients. In healty individuals, these cells differentiate into maccrophages, dendritic cells and neutrophils, but the tumors secrete a range of factors that disrupt diffentiation of immune progenitor cells (Ostrand- Rosenberg, 2008). As shown for isolated MSD cells from the peripheral blood and the spleensof healty mice, the MDS cells express the C5a receptor on their surface to a similar extent - anabundant expression - to that of their mature counterparts granulocytes and monocytes. As wellin tumor bearing mice, the MDS cells express the C5a receptor, but the expression level is lower on the surface of tumor associated MSD cells than on MSD cells in the peripheral blood and spleen. The reason is that the C5a receptor is internatilzed in tumor associated cells as shown by Markiewski et al, a C5a receptor antagonist can block the function of the C5a receptor on the surface of the MSD cells and led to an impaired tumor growth (Markiewski et al. 2008). C5a also acts as a suppressor of natural killer cell (NK cell) functions providing an explanation for negative impact of complement on tumor surveillance and NK function disorders in patientswith certain immune diseases (Li et al. 2012; Min et al. 2012).Inhibition of C5a signaling has been shown to have synergistic effects with other anti-cancer treatments, such as immunotherapy, preferably inhibition of the immune checkpoint moleculePD-1 (Ajona et al., 2017; Zha et al., 2017), chemotherapy (Medler et al., 2018), andradiotherapy (Beach et al., 2023; Yuan et al., 2023; O’Brian et al. 2024). Further inhibition ofC5a signaling has been shown to reverses resistance to anti-cancer treatments, such aschemotherapy (Su et al., 2018; Li et al. 2021) and PARP inhibition (Li et al., 2024).Accordingly, disease and / or disorders and / or diseased conditions for the treatment and / or prevention of which the medicament according to the present invention may be used include, but are not limited to tumor associated diseases and / or disorders and / or diseased conditions.In a preferrred embodiment, tumor or tumour is the name for a swelling or lesion formed by anabnormal growth of cells (termed neoplastic). A tumor can be benign, pre-malignant or malignant tumor. Moreover a tumor can be a solid tumor, preferably carcininoma, sarcomaa, aoteoma, fibrosarcoma, and chondrosoma The tumors which can in particular be treated by a medicament or a C5a binding agent,preferably a nucleic acid molecule according to the present invention, are preferably thosetumors which are selected from the group comprising tumors of the endocrine system, the eye, the gastrointestinal tract, the genital system, the haematopoietic system (including mixed and embryonic tumours), the mammary gland, the nervous system, the respiratory system, the skeleton, the skin, the soft tissues, the urinary outflow systemPreferably, these tumors are selected from the group comprising breast cancer (Su et al., 2018;Li et al., 2024), head and neck cancer (Gadwa et al., 2021), lung cancer (Ajona et al., 2017;Ortiz-Espinosa et al., 2022; Yuan et al., 2023), ovarian cancer (Zhang et al. 2023), cervicalcancer (Markiewski et al., 2008), prostate carcinoma (Imamura et al., 2021), osteosarcoma,glioblastoma (Lim et al., 2020), melanoma, colon cancer (Piao et al., 2015), and pancreaticneuroendocrine cancer (Contractor et al., 2016), small-cell lung carcinoma, colorectal carcinoma, hepatocellular carcinoma (Yeung et al., 2021), renal cancer (Yang et al., Int J Biol Markers 2023 Jun;38(2)) and myeloma such as multiple myeloma (Xiong et al., 2021),. It is within the present invention that the medicament and pharmaceutical composition, resepectively, containing a C5a binding agent, preferably a nucleic acid according to the presentinvention, may be used for the treatment in such way.In a further embodiment, the medicament comprises a further pharmaceutically active agent for the treament of tumors. Such further pharmaceutically active compounds are, among others but not limited thereto, those known to antineoplastic-active substances as alkylating agents, antimetabolites, antiangiogenic agents, mitose inhibiting agents, topoisomerase inhibitors, inhibitors of the cellular signal transduction, hormones, antibodies, immune conjugates and fusion proteins. Other pharmaceutically active compounds are, among others but not limited thereto, those known to Bleomycin, inhibitors of thymidylatsynthase such as Raltitrexed and Pemetrexed, enzymes such as L-asparaginase, Miltefosin and ANAgrelid, inhibitors of the proteasome such as Bortezomib. Moreover, the medicament according to the present invention may be used for the treatment and / or prevention of chronic obtructive pulmonary disease.Chronic obstructive pulmonary disease (abbr. COPD) is a lung ailment that is characterized bya persistent blockage of airflow from the lungs. It is an under-diagnosed, life-threatening lung disease that interferes with normal breathing and is not fully reversible. COPD includes a few lung diseases: the most common are chronic bronchitis and emphysema. Many people with COPD have both of these diseases. The emphysema is a damage to the air sacs at the tips of the airways what makes it hard for the body to take in the oxygen it needs. During chronic bronchitis the airways are irritated, red, and make too much sticky mucus. The walls of the airways are swollen and partly block the air from passing through. Neutrophils are attracted towards a C5a gradient, release superoxide radicals to kill pathogens and release beta-glucuronidase to hydrolyse complex glucuronide conjugates at the site of inflammation. However, these valuable defense mechanisms can be damaging to the body if the neutrophils are recruited to sites of pathogen-free inflammation, e.g. at reperfused sites afterinfaction, stroke (for example acute ischemic stroke, Keragala et al., 2020) or organtransplantation or in cases of autoimmune disease, alzheimer's disease and others that are listed below.In turn, excessively high C5a concentrations - especially if they are not only locally elevated asthey appear during sepsis - lead to a systemic activation of the neutrophils (leading to organdamage) with subsequent exhaustion and deactivation by means of reduced C5a receptor expression on the neutrophils' cell surface. This renders the patient even more vulnerable to thepathogens that persist in his body (Huber-Lang et al. 2002).A C5a binding agent, preferably a C5a-binding nucleic acid, that is also inhibitory for the C5a-mediated effects on its receptor (CD88) (as shown by chemotaxis assays using differentiated BAF-3 cells) has therefore the potenital to block the above named consequences of C5a signaling and could prove beneficial as part of a medicament in a number of diseases and conditions which aberrant C5a signaling is implicated in. One of these conditions is polymicrobial sepsis. There is a rich body of literature collecting evidence for the detrimental role of C5a signaling in sepsis (Ward 2010b). Nucleic acids according to the present inventions were found to improve survival of mice and organ function parameters in cecal ligation and puncture (CLP) studies. CLP is a well-established rodent model for polymicrobial sepsis. Recently the role of complement C5 in sepsis induced by cecal ligation and puncture wasinvestigated in wild-type and C5-deficient mice (Flierl et al. 2008). C5- / - mice had no survivaladvantage compared to WT mice and displayed a 400-fold increase of blood-borne bacteria when compared to wild-type mice. These effects were linked to the inability of C5 (- / -) mice to assemble the terminal membrane attack complex (MAC). The authors conclude that, during sepsis, selective blockade of C5a or its receptor (rather than C5) seems a more promising strategy, because C5a-blockade still allows for MAC formation while the adverse effects of C5a are prevented. In agreement, genetic deletion of C5a receptors CD88 and C5L2, pharmacological blockade of CD88 or pharmacological neutralization of C5a has been shownto be protective in cecal ligation and puncture (CLP) -induced sepsis (Czermak et al. 1999;Rittirsch et al. 2008). A translational in vitro model of meningococcal sepsis using humanwhole blood confirms that selective C5a inhibition (in contrast to blockade of C5 cleavage) prevents potentially harmful leukocyte activation without comprising bacterial clearance(Sprong et al. 2003). Inhibition of C5a prevents multiorgan failure in experimental sepsis bylimiting systemic inflammation, coagulation and other pathogenic mechanisms (Huber-Lang etal. 2001; Huber-Lang et al. 2002; Laudes et al. 2002; Rittirsch et al. 2008; Ward 2010a). Thenucleic acids according to this invention, though binding to C5 do not block C5 cleavage to C5a and C5b which is required for MAC formation. On the contray, the inventive nucleic acids occupy the protein C5, which also increases terminal plasma half-life and selectively block the action of C5a once this has been liberated, e.g. by the C5 convertase. In a sepsis model, nucleic acids according to this invention have been shown to limit inflammation, prevent multi organ failue and edema formation and to improve survival. Sepsis patients often require mechanical ventilation due to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). ALI / ARDS may also develop from a direct infection ofthe lung by community- or hospital-acquired infections in pneumonia. There is abundantevidence for a pathogenic role of C5a in ALI / ARDS. C5a induced tissue factor expressioncontributes to fibrin deposition within pulmonary alveoli of ALI / ARDS patients (Kambas et al.2008). Experimental ALI is attenuated in C5- / - mice and C5a-neutralisation or silencing ofC5aR in the lungs suppresses the inflammatory response and prevents vascular leakage (Bosmann & Ward 2012). In vivo pharmacological activity of C5a binding L-aptamers were tested in several mouse disease models and readouts. The involvement of C5a in the respective pathogenic mechanism was proven by blocking C5a’s effect by the C5a binding L-aptamers. Blocking C5a levels has been shown to improve outcome of viral and bacterial lung infections in animal models. The C5a binding L-aptamers have been shown to improve lung function in bacterial pneumonia and ventilator-induced lung injury models and to reduce extrapulmonary organ damage in bacterial pneumonia. They also improved outcomes in a polymicrobial sepsis model. Nonclinical efficacy has been shown in further disease models including lung cancer (in combination with immunotherapy), lung transplant rejection, diabetic nephropathy, and others as presented below: In a mouse model of Streptococcus pneumoniae-induced pneumonia, C5a blockade by a C5a binding L-aptamer reduced lung injury assessed by measuring pulmonary permeability 48 h after the infection. This was associated with less clinical symptoms of severe disease compared to vehicle treated animals (Muller-Redetzky, H., et al., 2020). In a complementary model with the same dose levels of the C5a binding L-aptamer, a single IP dose of was further able to limit the negative impact of mechanical ventilation on lung integrity (Muller-Redetzky, H., et al., 2020). Pneumonia-induced liver injury was assessed by histology and measurement of plasma aspartate aminotransferase (AST) levels 48 hours after infection and treatment with C5a binding L-aptamer or vehicle. Fibrin deposition, indicating a severe disruption of the local microcirculation and caspase 3 expression, indicating hepatocyte apoptosis were significantly reduced by treatment with C5a binding L-aptamer. A liver protective effect was confirmed by a normalization of plasma AST levels at both test doses (Muller-Redetzky, H., et al., 2020). In a mouse model of abdominal sepsis, C5a binding L-aptamer reduced local and systemic inflammation. Multiorgan damage, assessed by measuring serum markers of liver injury (ALT), kidney injury (creatinine and blood urea nitrogen) and general tissue damage (lactatedehydrogenase), was attenuated. Ten-day survival was increased with delayed treatmentinitiation of up to 6 hours after sepsis induction (Hoehlig, K., et al.2013). Evidence for the prevention of intravascular coagulation by C5a binding L-aptamer treatment was provided in a model of lung allograft rejection (Khan, M.A., et al., 2013). In this model, elevated levels of C5a were associated with the presence of prothrombotic factors in damaged microvessels. Treatment with C5a binding L-aptamer significantly reduced the vascular deposition of thrombin and tissue factor resulting in reduced microvascular injury and improved tissue oxygenation. The effect of C5a’s blockade by C5a binding L-aptamers were also shown in the following animal models: Model Key findings ReferenceLung transplant rejection improved tissueKhan, M.A., et al., 2013 oxygenation, limited Khan, M.A., et al, 2018 microvascular leakiness, prevention of airway ischemia and fibrosis, maintenance of healthy epithelium Lung cancer Synergistic effect of C5aAjona, D., et al., 2017 binding L-aptamer and anti PD-1 in attenuating tumour growth and metastasis in models resistant to anti-PD- 1 (V) monotherapy Lung cancer Reduction of boneAjona, D., et al., 2018 metastasis Duchenne muscular Reduced necrotic fibres Hyzewicz, J., et al., 2017. dystrophy associated with increased grip strength Diabetic nephropathy Improved renal lipidYiu, W.H., et al., 2018 metabolism with reduced serum triglyceride levels. Attenuated renal damage. Hematopoietic stem cell Mechanistic study: HSPC Bujko, K., et al., 2017 mobilization (=hematopoietic stem and progenitor cell) mobilization by G-CSF is reduced by C5a binding L-aptamer. Cardiomyopathy Reduced myocardialMavroidis, M, et al, 2015 remodelling and fibrosis Acute kidney injury Reduced renal neutrophilNot published infiltration. Reduced mortality Sterile liver inflammation Ameliorated livery injuryNot published with reduced granulocyte infiltration, ALT release and necrosis Age-related macular Decreased vascular leakage, Brockmann, C., et al., degeneration CNV (choroidal 2015. neovascularization) area and infiltration of CD11b+ cells Polytrauma and Reduced PMN effector Chakraborty, S., et al., 2021 haemorrhagic shock functions but no effect on lung damage. Cholesterol crystal Prevention and resolving of Zhao, D., et al., 2024 embolism (CCE) in CCE-induced AKI by atherosclerosis preventing immunothrombosis and ischemic necrosis. Allergy Reduced airway allergicRadhouani, M., et al., 2025 reaction following sensitization by skin infection. Moreover, other disease and / or disorders and / or diseased conditions for the treatment and / or prevention of which the medicament according to the present invention may be used include, but are not limited to are autoimmune diseases such as rheumatoid arthritis (abbr. RA), ankylosing spodylitis (abbr. AS), systemic lupus erythematosus (abbr. SLE), multiple sclerosis (abbr. MS), psoriasis, alopecia areata, warm and cold autoimmune hemolytic anemia (abbr. AIHA), atypical haemolytic uremia, pernicious anemia, acute inflammatory diseases, autoimmune adrenalitis, chronic inflammatory demyelinating polyneuropathy (abbr. CIDP), Churg-Strauss syndrome, Cogan syndrome, CREST syndrome, pemphigus vulgaris and pemphigus foliaceus, bullous pemphigoid, polymyalgia rheumatica, polymyositis, primary biliary cirrhosis, pancreatitis, peritonitis, psoriatic arthritis, rheumatic fever, sarcoidosis, Sjörgensen syndrome, scleroderma, celiac disease, stiff-man syndrome, Takayasu arteritis, transient gluten intolerance, autoimmune uveitis, vitiligo, polychondritis, dermatitis herpetiformis (abbr. DH) or Duhring's disease, fibromyalgia, Goodpasture syndrome, Guillain- Barré syndrome, Hashimoto thyroiditis, autoimmune hepatitis, inflammatory bowel disease (abbr. IBD), Crohn's disease, colitis ulcerosa, myasthenia gravis, immune complex disorders, glomerulonephritis, polyarteritis nodosa, anti-phospholipid syndrome, polyglandular autoimmune syndrome, idiopatic pulmonar fibrosis, idiopathic thrombocytopenic purpura(abbr. ITP), urticaria (Yanase et al., 2021; Kocatürk et al., 20172017), autoimmune infertility,juvenile rheumatoid arthritis, sarcoidosis, autoimmune cardiomyopathy, Lambert-Eaton syndrome, lichen sclerosis, Lyme disease, Graves disease, Behçet's disease, Ménière's disease,reactive arthritis (Reiter's syndrome); infections with viruses such as HIV (Bertacchi et al.,2022), HBV, HCV, CMV or intracellular parasites such as Leishmania, Rickettsia, Chlamydia, Coxiella, Plasmodium, Brucella, mycobacteria, Listeria, Toxoplasma and Trypanosoma; secondary damages of trauma; local inflammation, shock, anaphylactic shock, burn, septic shock, haemorrhagic shock, systemic inflammatory response syndrome (abbr. SIRS), multiple organ failure (abbr. MOF), asthma and allergy, vasculitides such as arteritis temporalis, vasculitis, vascular leakage, and atherosclerosis; acute injuries of the central nervous system, myocarditis, dermatomyositis, gingivitis, acute respiratory insufficiency, chronic obstructivepulmonary disease, stroke, myocardial infarction, reperfusion injury such as ischemicreperfusion (Thorenz et al., 2018; Zhang et al. (b) 2021; Holste et al., 2021) or myocardialischemia reperfusion injury (Asare et al., 2024; Huang et al., 2021), neurocognitive dysfunction, burn, inflammatory diseases of the eye such as uveitis, age-related macular degeneration (abbr. AMD; Gotfredsen et al., 2025), diabetic retinopathy (abbr. DR), Purtscher retinopathy (Rotuski, 2024), diabetic macular edema (abbr. DME), ocular pemphigoid, keratoconjunctivitis, Stevens-Johnson syndrome, and Graves ophthalmopathy; localmanifestations of systemic diseases, inflammatory diseases of the vasculature, acute injuries ofthe central nervous system, type 1 and 2 diabetes, the manifestations of diabetes, SLE, and rheumatic disease in the eye, brain, vasculature, heart, lung, kidneys, liver, gastrointestinal tract, spleen, skin, bones, lymphatic system, blood or other organ systems, for the prevention and / or support and / or post-operative treatment of coronary artery bypass graft (abbr. CABG), off- pump coronary artery bypass graft (abbr. OPCABG), minimally invasive direct coronary artery bypass graft (abbr. MIDCAB), percutaneous transluminal coronary angioplasty (abbr. PTCA), thrombolysis, organ transplantation, and vessel clamping surgery; for the prevention of organdamage of a transplanted organ or of an organ to be transplanted or for use of treatment oftransplant rejection for transplanted organs such as liver, kidney, intestine, lung, heart, skin, limb, cornea, Langerhans islet, bone marrow, blood vessels and pancreas; fetal rejection. The various diseases and disorders for the treatment and / or prevention of which C5a bindingagent, preferably a nucleic acid, can be used, may be grouped as follows:1. Autoimmune / inflammatory diseases1.1 Systemic autoimmune and / or inflammatory diseases comprising allergy, septic shock, secondary damages of trauma, warm and cold autoimmune hemolytic anemia (abbr. AIHA), systemic inflammatory response syndrome (abbr. SIRS), hemorrhagic shock, diabetes type 1, diabetes type 2, the manifestations of diabetes, diffuse scleroderma, periodontitis and its associates bone loss, polychondritis, polyglandular autoimmune syndrome, rheumatoid arthritis, systemic lupus erythematosus (abbr. SLE) and manifestations thereof, reactive arthritis(also known as Reiter's syndrome) and alcohol-associated hepatitis (Fan et al., Hepatology.2021 Mar;73(3):983-997). 1.2 Autoimmune and / or inflammatory diseases of the gastro-intestinal tract comprising Crohn's disease, colitis ulcerosa, celiac disease, transient gluten intolerance, inflammatorybowel disease (abbr. IBD), pancreatitis (Jung et al., 2020), gastrointestinal allergichypersensitivity, necrotizing enterocolitis, CHAPLE syndrome (Ozsen et al., N Engl J Med. 2017 Jul 6;377(1):52-61). 1.3 Autoimmune and / or inflammatory diseases of the skin comprising psoriasis, urticaria (Yanase et al., 2021; Kocatürk et al., 2017 2017), dermatomyositis, pemphigus vulgaris,pemphigus foliaceus, bullous pemphigoid, morphea / linear scleroderma, vitiligo, dermatitisherpetiformis (abbr. DH) or Duhring's disease, lichen sclerosis. 1.4 Autoimmune and / or inflammatory diseases of the vasculature comprising vasculitides (preferably arteritis temporalis), vasculitis, Henoch Schönlein purpura, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, vascular leakage, polymyalgia rheumatica, atherosclerosis, Churg-Strauss syndrome, Takayasu arteritis, Goodpasture syndrome (= antiglomerular basement membrane disease; mostly affecting the kidneys glomeruli and the lungs), glomerulonephritis, polyarteritis nodosa, Behçet's disease, aneurysmal subarachnoid hemorrhage (SAH) (Koopman et al, Trials (2020) 21:969; Otsuka et al. Journal of Neuroimmunology 357 (2021) 577610)1.5 Autoimmune and / or inflammatory diseases of the nervous system comprising multiplesclerosis (abbr. MS), chronic inflammatory demyelinating polyneuropathy (abbr. CIDP), peripheral neuropathy (Giorgio et al., Biomedicines. 2021 Apr 7;9(4):399), neurocognitive dysfunction, stiff-man syndrome, Guillain-Barré syndrome, myasthenia gravis, Lambert-Eaton syndrome, neuromyelitis optica (Devic syndrome). 1.6 Muscular skeletal autoimmune and / or inflammatory diseases comprising rheumatoid arthritis, rheumatic disease in the eye, brain, lung, kidneys, heart, liver, gastrointestinal tract, spleen, skin, bones, lymphatic system, blood or other organs, ankylosing spodylitis (abbr. AS), sarcoidosis, periodontitis and associated bone loss, polymyalgia rheumatica, polymyositis,psoriatic arthritis, rheumatic fever, polychondritis, fibromyalgia, Duchenne musculardystrophy, juvenile rheumatoid arthritis, Lyme disease, reactive arthritis (also known as Reiter'ssyndrome), gout (Wessig et al., Sci Rep.2022 Mar 16;12(1):4483). 1.7 Other autoimmune and / or inflammatory diseases comprise Cogan syndrome , autoimmune adrenalitis, immune complex disordes, Ménière's disease, local inflammations, alopecia areata, acute inflammatory diseases, primary biliary cirrhosis, Sjörgen’s syndrome, scleroderma, diffuse scleroderma, CREST syndrome, Morphea / linear scleroderma, autoimmune uveitis, Hashimoto thyroiditis (autoimmune thyroid destruction), Graves disease, autoimmune hepatitis, non-alcoholic steatohepatitis, glomerulonephritis, peritonitis,(catastrophic) anti-phospholipid syndrome (Aguiar & Erkan, Ther Adv Musculoskel Dis (2013)5(6) 305–314), lung fibrosis (Zhu et al., Ecotoxicol Environ Saf. 2025 Jan 1;289:117627),idiopathic pulmonary fibrosis, interstitial lung disease (Osthoff et al., Arthritis Res Ther. 2019Mar 18;21(1); Maher .JAMA. 2024 May 21;331(19):1655-1665), drug-induced interstitial lungdisease (DIILD) (see below), pneumonitis (see below), renal fibrosis, hepatic fibrosis, autoimmune infertility, fetal rejection or miscarriage and graft-versus-host disease. 2. Diseases of the eye comprising uveitis, conjunctivitis, age-related macular degeneration(abbr. AMD) (Brockmann et al., 2015), diabetic retinopathy (abbr. DR), Purtscher retinopathy(Rotuski, 2024), diabetic macular edema (abbr. DME), retinal vessel occlusion, glaucoma, cataract, autoimmune retinal and intraocular inflammatory disease, ocular pemphigoid, keratoconjunctivitis, Stevens-Johnson syndrome, and Graves ophthalmopathy. 3. Reperfusion injuries and transplant rejections comprising stroke, myocardial infarction, reperfusion injuries, posttransplant thrombotic microangiopathy (Brocklebank et al,.2018 ).)ororgan damage to transplanted organs, such as lung, liver (Arumugam et al. 2004), kidney(Arumugam et al. 2003), intestine, lung, heart, skin, limb , cornea, islets of Langerhans(Tokodai et al. 2010), bone marrow, blood vessels and pancreas, kidney damage after organ orbone marrow transplantation. 4. Prevention of transplant rejection comprising transplant rejection of transplanted organs, such as liver, kidney, intestine, lung, heart, skin, limb, cornea, islets of Langerhans, bone marrow, blood vessels and pancreas.5. Cardiovascular diseases comprising atherosclerosis (Dewan et al., FEBS Open Bio.2021 May;11(5):1374-1381) and manifestations thereof, e.g. cholersterol crystal embolism(Zhao, D., et al., Kidney Int, 2024. 106(5):819-825), myocarditis, cardiomyopathy, myocardialinfarction, stroke, pulmonary arterial hypertension (PAH), Abdominal Aortic Aneurism, inflammatory diseases of the vasculature, vasculitides, preferably arteritis temporalis, vasculitis, vascular leakage, the manifestations of diabetes, pre-eclempsia, autoimmune cardiomyopathy, vein hostdisease, arrythmogenic right ventrivular dysplasia / cardiomyopathy (Ren et al., 2021), for theprevention and / or support and / or post-operative treatment of coronary artery bypass graft (abbr. CABG). 6. Metabolic dysfunction comprising insulin resistance, glucose intolerance, adipose inflammation, diabetic nephropathy, diabetic kidney disease (Budge et al., Front Med (Lausanne).2021 Jan 21;7:599236.. eCollection 2020; Tan et al., Diabetes.2020 Jan;69(1):83- 98; Ort et al., Front Immunol. 2020 Dec 10;11:599417), polycystic ovary syndrome (PCOS)(Lewis et al. (b), Clin Endocrinol (Oxf). 2021 Jan;94(1):74-84) and cardiovascular dysfunctionin diet-induced obesity. 7. Respiratory diseases comprising asthma, acute respiratory insufficiency, acute lung injury, transfusion related lung injury, adult respiratory distress syndrome, chronic obstructive pulmonary disease, ventilator-induced lung injury, pneumonia (such as necrotizing pneumonia[Harada et al., 2021 ;; Chow et al., 2020]) and complications thereof, e.g. acute kidney injury(AKI) (Devarajan, Curr Opin Pediatr. 2023 Apr 1;35(2):234-238), acure liver failure (see below) or stroke. 8. Inflammatory diseases comprising inflammatory disease of the eye, autoimmune uveitis(Copland et al. 2010), conjunctivitis, vernal conjunctivitis, local manifestations of systemicdiseases. 9. Acute reactions comprising secondary damages of trauma and fractures, e.g. complex regional pain syndrome (Shi et al., Pain. 2021 May 1;162(5):1400-1415), shock, burn, anaphylactic shock, hemorrhagic shock, multiple organ failure (abbr. MOF), acute injuries of the central nervous system,spinal cord injury (Shibata et al, J Neurotrauma.2022 May;39(9- 10):667-682), acute damage due to excessive C5a production by an activated coagulation system such as after organ or islet transplantation,10. Pain, acute pain, chronic pain, neuropathic pain (Spera et al., 2022; Shi et al., ),morphine tolerance and withdrawal-induced hyperalgesia, e.g. complex regional pain syndrome (see above), chemotherapy-induced neuropathy (Spera et al., 2022).11. Neurological and neurodegenerative disorders comprising neuropathies, AmyotrophicLateral Sclerosis (ALS), Alzheimer’s disease and Parkinson’s disease (Farkas et al.1998). 12. Infectious diseases comprising12.1 bacterial infections, preferably meningitis (Muenstermann et al., 2019), Lyme disease,reactive arthritis (also known as Reiter's syndrome), urinary tract and kidney infection (Wu etal.,.2022), sepsis and its complications such as organ failure, e.g. acute liver failure (Kusakabe et al., 2021;11(5):1351-1367). aHUS (see below) or AKI (see above), cardiac dysfunction, systemic hypoperfusion, acidosis, acute respiratory distress syndrome, acute lung injury (ALI), infections with intracellular pathogens (Klos et al.2009),12.2 viral infections, preferably HIV (Bertacchi et al., Biomolecules. 2022 Feb15;12(2):313), HBV, HCV, CMV, viral meningitis, COVID-19 (Senent et al.2021; Tsai et al2023) and their complications, such as sepsis and its complications (see above), 12.3 intracellular parasites, preferably Leishmania, Rickettsia, Chlamydia, Coxiella, plasmodium, especially cerebral malaria, Brucella, mycobacteria, Listeria, Toxoplasma and Trypanosoma. 13. Hematological diseases comprising diseases associated with activation of coagulationand fibrinolytic systems disseminated intravascular coagulation (DIC) and / or thrombosis (Chenet al. (b) 2022), pernicious anemia, warm and cold autoimmune hemolytic anemia (abbr.AIHA), anti-phospholipid syndrome and its associated complications, arterial and venous thrombosis, pregnancy complications such as recurrent miscarriage and fetal death, preeclampsia, placental insufficiency, fetal growth restriction, cervical remodeling and pretermbirth, idiopathic thrombocytopenic purpura (abbr. ITP), atypical hemolytic uremic syndrome(aHUS; Gastoldi et al.; 2022), paroxysmal nocturnal hemoglobinuria (PNH) and allergic transfusion reactions.14. Clinical complications associated with activation by biomaterials of complement andcoagulation cascades occurring in procedures comprising hemodialysis (such as renal failure inthe case of a dialysis; Melchior, 2021), infusion of nanoparticles, i.e. complement-mediated infusion reactions (Maisha et al., 2021), apheresis, visco-supplementation of arthritic joints,cardiopulmonary bypass, prosthetic vascular grafts and use of cardiovascular devices. Anexample is cholesterol chrystal embolism (Zhao et al., 2024), which may, also occur spontaneously in patients with cholesterol-rich intravascular plaques.15. Poisoning or clinical complications elicited by other therapeutics, procedures orvaccines, e.g. envenomation / venom poisoning (De France et al., 2021), doxorubicin-induced cardiomyocyte senescence (Wen et al., 2021), Nephrotoxicity of cisplatin (Huang S et al., 2019), drug-induced interstitial lung disease (DIILD), (Conte et al.,.2022), immune checkpoint inhibitor-induced pneumonitis (Naidoo et al.,. 2020), TRALI: transfusion-related acute lung injury (van der Velden et al., 2024; Jongerius et al., 2019); vaccine hypersensitivity reactions (Lim et al (b)., 2023.16. Illnesses following exposure to radiation (i.e. induction of radioresistance) (Beach et al.,J 2024; O’Brian et al., 2024) .17. Decompression sickness (DCS), ( Thompson et al.. 2020)18. Cancer, preferably tumors of lung (Corrales et al., 2012, Cho et al., 2014), ovary (Cho et al., 2014), liver (Cho et al., 2014), kidney (Cho et al., 2014), endometrium (Cho et al., 2014),and thyroid gland (Lucas et al., 1996), lung cancer (Ajona et al., 2015), ovarian cancer (Bjorgeet al., 2005), breast cancer (Su et al., 2018; Li et al., 2024), head and neck cancer (Gadwa et al., 2021), lung cancer (Ajona et al., 2017; Ortiz-Espinosa et al., 2022; Yuan et al., 2023 ), ovary carcinoma, ovarian cancer (Zhang et al. 2023), cervical cancer (Markiewski et al., 2008), prostate carcinoma (Imamura et al., 2021), osteosarcoma, glioblastoma (Lim et al., 2020), melanoma, colon cancer (Piao et al., 2015), pancreatic neuroendocrine cancer (Contractor et al., 2016), small-cell lung carcinoma , and colorectal carcinoma, hepatocellular carcinoma (Yeung et al., 2021), renal cancer (Yang et al., Int J Biol Markers 2023 Jun;38(2)) and myeloma such as multiple myeloma (Xiong et al., 2021).The C5a binding agent, preferably a nucleic acid according to the present invention, may alsobe used in an intra-operative manner to avoid deleterious effects of the patient’s immunesystem, more preferably for the prevention and / or support and / or post-operative treatment ofcoronary artery bypass graft (abbr. CABG), off-pump coronary artery bypass graft (abbr. OPCABG), minimally invasive direct coronary artery bypass graft (abbr. MIDCAB), percutaneous transluminal coronary angioplasty (abbr. PTCA), thrombolysis, organtransplantation, brain and spinal cord surgery, reconstructive surgery, and vessel clampingsurgery, during any treatment with artificial ventilation or ventilation assistance to avoid lung ventilator-induced lung injury or secondary damages, such as vascular leakage and / oremphysema, for the prevention of organ damage of a transplanted organ or of an organ to betransplanted or for use of treatment of transplant rejection and reperfusion injury for transplanted organs, such as liver, kidney, intestine, lung, heart, skin, limb, cornea, islets of Langerhans, bone marrow, blood vessels and pancreas. It is within the present invention that the medicament and pharmaceutical composition, resepectively, containing a nucleic acid according to the present inventors may be used for the treatment in such way. In a further embodiment, the medicament comprises a further pharmaceutically active agent. Such further pharmaceutically active compounds are, among others but not limited thereto, those known to suppress the immune system such as calcineurin inhibitors, cyclosporin A, methotrexate, azathioprin, tacrolimus, rapamycin, chlorambucil, leflunomide, mycophenolate mofetil, brequinar, mizoribin, thalidomide, or deoxyspergualin. The further pharmaceutically active compound can be, in a further embodiment, also one of those compounds which reduce histamine production such as meclozin, clemastin, dimetinden, bamipin, ketotifen, cetirizin, lovecetirizin, cesloratadin, azelastin, mizolastin, levocabastin, terfenadin, fexofenadin, or ebastin. Such compounds can also be, but are not limited to, steroids and are preferably selected from the group comprising corticosteroids like prednisone, methylprednisolone, hydrocortisone, dexamethasone, triamcinolone, betamethasone, effervescent, or budesonide. Further, such compound can be one or several antibiotics such as, but not restricted to, aminoglycosides, β-lactam antibiotics, gyrase inhibitors, glycopeptide antibiotics, lincosamide, macrolide antibiotics, nitroimidazole derivatives, polypeptide antibiotics, sulfonamides, trimethoprim and tetracycline. Additionally, more specific anti-inflammatory or anti- angiogenic biologics can be used in combination such as bevacizumab, ranibizumab, IL-10, erlizumab, tolermab, rituximab, gomiliximab, basiliximab, daclizumab, HuMax-TAC, visilizumab, HuMaxCD4, clenoliximab, MAX 16H5, TNX 100, toralizumab, alemtuzumab, CY 1788, galiximab, pexelizumab, eculizumab, PMX-53, ETI 104, FG 3019, bertilimumab, 249417 (anti-factor IX) abciximab, YM 337, omalizumab, talizumab, fontolizumab, J695 (anti- IL12), HuMaxIL-15, mepolizumab, elsilimomab, HuDREG, anakinra, Xoma-052, adalimumab, infliximab, certolizumab, afelimomab, CytoFab, AME 527, Vapaliximab,bevacizumab, ranibizumab, vitaxin, belimumab, MLN 1202, volociximab, F200 (anti-α5β1),efalizumab, m60.11 (anti.CD11b), etanercept, onercept, rilonacept, abatacept, natalizumab, orsiplizumab, tocilizumab, ustekinumab, ABT-874. Finally, the further pharmaceutically active agent may be a modulator of the activity of any other chemokine which can be a chemokineagonist or antagonist or a chemokine receptor agonist or antagonist whereby the chemokine canalso be a chemotactic lipid. An example is the S1P receptor modulator fingolimod. Alternatively, or additionally, such further pharmaceutically active agent is a further C5a binding agent, preferably a nucleic acid according to the present invention. Alternatively, the medicament comprises at least one more C5a binding agent which binds to a target molecule different from C5a or exhibits a function which is different from the one of the nucleic acids according to the present invention. In general the C5a antagonist can be combined with inhibitors of other proinflammatory molecules or their receptors. Examples for proinflammatory molecules whose action can be attenuated in combination with the C5a antagonist are IL-1, IL-2, IL-5, IL-6, IL-8, IL-10, IL- 12, IL-13, IL-15, IL-16, IL-17, IL-18, IL-23, TNF, α4β7, α5β1, BlyS, cadherin, CCR2, CD11a, CD11b, CD125, CD130, CD16, CD18, CD2, CD20,CD22, CD23, CD25, CD28, CD3, CD30, CD4, CD40, CD40L, CD44, CD45R, CD54, CD62E, CD62L, CD68, CD8, CD80, CD86, CD95, CEP, gastrin-R, C1, C1-esterase, C5, factor D, MBL, complement receptor 1, CRTH2-receptor, CTGF, E- and P-selectin, eotaxin, factor IX, FGF-20, Fgl-2, GM-CSF, GP IIb / IIIareceptor, HMG1, ICAM-1, IgE, thymocytes, IFNγ, IFNr, IP-10, MCP-1, M-CSF receptor, MIF, MMP9, PDGF-D, SDF-1, TGFβ1, tissue factor, tyrosine kinase receptor, VAP-1, VCAM-1, VEGF, VLA1, von Willebrandt factor, sphingosine 1 Phosphate, ceramide-1 phopshate, and inibitors of mitogens, e.g. inhibitors of lysophosphatidic acid. Finally, the further pharmaceutically active agent may be a modulator of the activity of any other chemokine which can be a chemokine agonist or antagonist or a chemokine receptor agonist or antagonist. Alternatively, or additionally, such further pharmaceutically active agent is a further C5a binding agent . Alternatively, the medicament comprises at least one more C5a binding agent which binds to a target molecule different from C5a or exhibits a function which is different from the one of the nucleic acids according to the present invention. It is within the present invention that the medicament is alternatively or additionally used, in principle, for the prevention of any of the diseases disclosed in connection with the use of the medicament for the treatment of said diseases. Respective markers therefore, i.e. for the respective diseases are known to the ones skilled in the art. Preferably, the respective marker is C5a. In one embodiment of the medicament of the present invention, such medicament is for use in combination with other treatments for any of the diseases disclosed herein, particularly those for which the medicament of the present invention is to be used. "Combination therapy" (or "co-therapy") includes the administration of a medicament of the invention and at least a second agent as part of a specific treatment regimen intended to provide the beneficial effect from the co-action of these therapeutic agents, i. e. the medicament of the present invention and said second agent. The beneficial effect of the combination includes, but is not limited to, pharmacokinetic or pharmacodynamic co-action resulting from the combination of therapeutic agents. Administration of these therapeutic agents in combination typically is carried out over a defined time period (usually minutes, hours, days or weeks depending upon the combination selected). "Combination therapy" may, but generally is not, intended to encompass the administration of two or more of these therapeutic agents as part of separate monotherapy regimens that incidentally and arbitrarily result in the combinations of the present invention. "Combination therapy" is intended to embrace administration of these therapeutic agents in a sequential manner, that is, wherein each therapeutic agent is administered at a different time, as well as administration of these therapeutic agents, or at least two of the therapeutic agents, in a substantially simultaneous manner. Substantially simultaneous administration can be accomplished, for example, by administering to a subject a single capsule having a fixed ratio of each therapeutic agent or in multiple, single capsules for each of the therapeutic agents. Sequential or substantially simultaneous administration of each therapeutic agent can be effected by any appropriate route including, but not limited to, topical routes, oral routes, intravenous routes, intramuscular routes, and direct absorption through mucous membrane tissues. The therapeutic agents can be administered by the same route or by different routes. For example, a first therapeutic agent of the combination selected may be administered by injection while the other therapeutic agents of the combination may be administered topically. Alternatively, for example, all therapeutic agents may be administered topically or all therapeutic agents may be administered by injection. The sequence in which the therapeutic agents are administered is not narrowly critical unless noted otherwise. "Combination therapy" also can embrace the administration of the therapeutic agents as described above in further combination with other biologically active ingredients. Where the combination therapy further comprises a non-drug treatment, the non-drug treatment may be conducted at any suitable time so long as a beneficial effect from the co-action of the combination of the therapeutic agents and non-drug treatment is achieved. For example, in appropriate cases, the beneficial effect is still achieved when the non-drug treatment is temporally removed from the administration of the therapeutic agents, perhaps by days or even weeks. As outlined in general terms above, the medicament according to the present invention can be administered, in principle, in any form known to the ones skilled in the art. A preferred route of administration is systemic administration, more preferably by parenteral administration, preferably by injection. Alternatively, the medicament may be administered locally. Other routes of administration comprise intramuscular, intraperitoneal, and subcutaneous, per orum, intranasal, intratracheal or pulmonary with preference given to the route of administration that is the least invasive, while ensuring efficiancy. Parenteral administration is generally used for subcutaneous, intramuscular or intravenous injections and infusions. Additionally, one approach for parenteral administration employs the implantation of a slow-release or sustained-released systems, which assures that a constant level of dosage is maintained, that are well known to the ordinary skill in the art. Furthermore, preferred medicaments of the present invention can be administered in intranasal form via topical use of suitable intranasal vehicles, inhalants, or via transdermal routes, using those forms of transdermal skin patches well known to those of ordinary skill in that art. To be administered in the form of a transdermal delivery system, the dosage administration will, of course, be continuous rather than intermittent throughout the dosage regimen. Other preferred topical preparations include creams, ointments, lotions, aerosol sprays and gels, wherein the concentration of active ingredient would typically range from 0.01% to 15%, w / w or w / v. The medicament of the present invention will generally comprise an effective amount of theactive component(s) of the therapy, including, but not limited to, a C5a binding agent preferablya nucleic acid molecule of the present invention, dissolved or dispersed in a pharmaceutically acceptable medium. Pharmaceutically acceptable media or carriers include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like. The use of such media and agents for pharmaceutical active substances is well known in the art. Supplementary active ingredients can also be incorporated into the medicament of the present invention.In a further aspect the present invention is related to a pharmaceutical composition. Suchpharmaceutical composition comprises at least one of the C5a binding agent, preferably anucleic acid according to the present, invention and preferably a pharmaceutically acceptablevehicle. Such vehicle can be any vehicle or any binder used and / or known in the art. More particularly such binder or vehicle is any binder or vehicle as discussed in connection with the manufacture of the medicament disclosed herein. In a further embodiment, the pharmaceutical composition comprises a further pharmaceutically active agent. The preparation of a medicament and a pharmaceutical composition will be known to those of skill in the art in light of the present disclosure. Typically, such compositions may be prepared as injectables, either as liquid solutions or suspensions; solid forms suitable for solution in, or suspension in, liquid prior to injection; as tablets or other solids for oral administration; as timerelease capsules; or in any other form currently used, including eye drops, creams, lotions,salves, inhalants and the like. The use of sterile formulations, such as saline-based washes, by surgeons, physicians or health care workers to treat a particular area in the operating field may also be particularly useful. Compositions may also be delivered via microdevice, microparticle or sponge. Upon formulation, a medicament will be administered in a manner compatible with the dosage formulation, and in such amount as is pharmacologically effective. The formulations are easily administered in a variety of dosage forms, such as the type of injectable solutions described above, but drug release capsules and the like can also be employed. In this context, the quantity of active ingredient and volume of composition to be administered depends on the individual or the subject to be treated. Specific amounts of active compound required for administration depend on the judgment of the practitioner and are peculiar to each individual. A minimal volume of a medicament required to disperse the active compounds is typically utilized. Suitable regimes for administration are also variable, but would be typified by initially administering the compound and monitoring the results and then giving further controlled doses at further intervals. For instance, for oral administration in the form of a tablet or capsule (e.g., a gelatin capsule),the active drug component, i. e. a C5a binding agent, preferably a nucleic acid molecule of thepresent invention, and / or any further pharmaceutically active agent, also referred to herein astherapeutic agent(s) or active compound(s) can be combined with an oral, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water and the like. Moreover, when desired or necessary, suitable binders, lubricants, disintegrating agents, and coloring agents can also be incorporated into the mixture. Suitable binders include starch, magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidone, natural sugars such as glucose or beta- lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth or sodium alginate, polyethylene glycol, waxes, and the like. Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, silica, talcum, stearic acid, its magnesium or calcium salt and / or polyethyleneglycol, and the like. Disintegrators include, without limitation, starch, methyl cellulose, agar, bentonite, xanthan gum starches, agar, alginic acid or its sodium salt, or effervescent mixtures, and the like. Diluents, include, e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine. The medicament of the invention can also be administered in such oral dosage forms as timed release and sustained release tablets or capsules, pills, powders, granules, elixirs, tinctures, suspensions, syrups and emulsions. Suppositories are advantageously prepared from fatty emulsions or suspensions. The pharmaceutical composition or medicament may be sterilized and / or contain adjuvants, such as preserving, stabilizing, wetting or emulsifying agents, solution promoters, salts for regulating the osmotic pressure and / or buffers. In addition, they may also contain other therapeutically valuable substances. The compositions are prepared according to conventional mixing, granulating, or coating methods, and typically contain about 0.1% to 75%, preferably about 1% to 50%, of the active ingredient. Liquid, particularly injectable compositions can, for example, be prepared by dissolving, dispersing, etc. The active compound is dissolved in or mixed with a pharmaceutically puresolvent such as, for example, water, saline, aqueous dextrose, glycerol, ethanol, and the like, tothereby form the injectable solution or suspension. Additionally, solid forms suitable for dissolving in liquid prior to injection can be formulated. For solid compositions, excipients include pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, talcum, cellulose, glucose, sucrose, magnesium carbonate, and the like. The active compound defined above, may be also formulated as suppositories, using for example, polyalkylene glycols, for example, propylene glycol, as the carrier. In some embodiments, suppositories are advantageously prepared from fatty emulsions or suspensions. The medicaments and C5a binding agent, preferably the nucleic acid molecules, respectively, of the present invention can also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles. Liposomes can be formed from a variety of phospholipids, containing cholesterol, stearylamine or phosphatidylcholines. In some embodiments, a film of lipid components is hydrated with an aqueous solution of drug to a form lipid layer encapsulating the drug, what is well known to theordinary skill in the art. For example, the C5a binding agent, preferably a nucleic acid moleculedescribed herein, can be provided as a complex with a lipophilic compound or non-immunogenic, high molecular weight compound constructed using methods known in the art. Additionally, liposomes may bear such nucleic acid molecules on their surface for targeting andcarrying cytotoxic agents internally to mediate cell killing. An example of nucleic-acidassociated complexes is provided in U.S. Patent No.6,011,020. The medicaments and C5a binding agent, preferably nucleic acid molecules, respectively, of the present invention may also be coupled with soluble polymers as targetable drug carriers. Such polymers can include polyvinylpyrrolidone, pyran copolymer, polyhydroxypropyl- methacrylamide-phenol, polyhydroxyethylaspanamidephenol, or polyethyleneoxidepolylysine substituted with palmitoyl residues. Furthermore, the medicaments and C5a binding agent, preferably nucleic acid molecules, respectively, of the present invention may be coupled to aclass of biodegradable polymers useful in achieving controlled release of a drag, for example,polylactic acid, polyepsilon capro lactone, polyhydroxy butyric acid, polyorthoesters,polyacetals, polydihydropyrans, polycyanoacrylates and cross- linked or amphipathic blockcopolymers of hydrogels. If desired, the pharmaceutical composition and medicament, respectively, to be administered may also contain minor amounts of non-toxic auxiliary substances such as wetting or emulsifying agents, pH buffering agents, and other substances such as for example, sodium acetate, and triethanolamine oleate. The dosage regimen utilizing the nucleic acid molecules and medicaments, respectively, of the present invention is selected in accordance with a variety of factors including type, species, age, weight, sex and medical condition of the patient; the severity of the condition to be treated; the route of administration; the renal and hepatic function of the patient; and the particular aptamer or salt thereof employed. An ordinarily skilled physician or veterinarian can readily determine and prescribe the effective amount of the drug required to prevent, counter or arrest the progress of the condition. Effective plasma levels of the nucleic acid according to the present invention preferably range from 500 fM to 500 µM in the treatment of any of the diseases disclosed herein. The nucleic acid molecules and medicaments, respectively, of the present invention may preferably be administered in a single daily dose, every second or third day, weekly, every second week, in a single monthly dose or every third month. It is within the present invention that the medicament as described herein constitutes the pharmaceutical composition disclosed herein. In a further aspect the present invention is related to a method for the treatment of a subject who is in need of such treatment, whereby the method comprises the administration of a pharmaceutically active amount of at least one of the nucleic acids according to the present invention. In an embodiment, the subject suffers from a disease or is at risk to develop such disease, whereby the disease is any of those disclosed herein, particularly any of those diseases disclosed in connection with the use of any of the nucleic acids according to the present invention for the manufacture of a medicament. As preferably used herein, the term treatment comprises in a preferred embodiment additionally or alternatively prevention and / or follow-up. As preferably used herein, the terms disease and disorder shall be used in an interchangeable manner, if not indicated to the contrary. As used herein, the term comprise is preferably not intended to limit the subject matter followed or described by such term. However, in an alternative embodiment the term comprises shall be understood in the meaning of containing and thus as limiting the subject matter followed or described by such term. In an embodiment of each and any aspect, including any embodiment thereof, and as preferablyused herein, a loading dose is an initial dose of a drug that is given at the beginning of a course of treatment before to establish a target drug level which is subsequently maintained by continuous infusion of the drug. Continuous infusion starts immediately after the loading dose has been administered. An assay for determing the inhibition of C5a and C5a activity is, for example, described in Example 8 or in Zelek et al. The various SEQ.ID. Nos., the chemical nature of the nucleic acid molecules according to the present invention and the target molecules C5a as used herein, the actual sequence thereof and the internal reference number is summarized in the following table.

[0007] C C C C C C C C G G C C C C C C C G G G G G G G G G G G G G G G G G G G G G A A G G G G G G G A A A A A A C C A A A A A A A C C C C C C A A C C C C C C C A A A A A d C C A A A A A A A C C C C C A G G C C C C C C C G G G G G C C C G G G G G G G C C C C C G A A C C C C C C C A A A A A C G G A A A A A A A G G G G G A C C G G G G G G G C C C C C G U U C C C C C C C U U U U U C G d U U U U U U U G G G G d U U G G G G G G G G U U U U G G d U U U U U U U U G G G d U U G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G U U U G G G U U G G U U G G G U U U U U U U U U U U U U U U G G G U U U G G G G G G G G G U U U G G G U U U U U U U U U U U U U U U U U U U U U U A C G G G U U U G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G G A A A G G G A A A G A A G G G A A A A A A A A A A A A A A A G G d A A A G G G G G G G G G U d G G G G U U U U U U U U U G U U U U U G G U U U G G G U G G G G G G G G G G G G G G G U G G G G G U U U U U U U U U G U U U U U G G G G G G G G G G G G G G G G G G G G G G G G U G G G G G U U U U U U U U U d U U U U U d d e G G G G G G G G G G G G G G G c U U U U U U U U U U U U U U U n A A A A A A A A A A A A A A A e G G G G G G G G G G G G G G G u U U U U U U U U U U U U U U U q C C C C C C C C C C C C C C C e C C C C C C C C C C C C C C C S G G G G G G G G G G G G G G G A A A A A A A A N N N N N N N N D D D D D D D D - - - - - - - - L L L L L L L L / / / / / / / / A A A A A A A A A A A A A A A N N N N N N N N N N N N N N N R R R R R R R R R R R R R R R - - - - - - - - - - - - - - - L L L L L L L L L L L L L L L e c 0 2 n 3 3 e - - r 4 9 6 7 0 2 0 9 9 e 1 ) 0 1 1 3 3 4 0 0 f G 1 D D D D D D D D e - 0 - - - - - - - - R 2 2 2 2 0 2 2 2 1 1 1 1 1 1 1 1 0 0 0 0 9 0 0 0 0 0 0 0 0 0 0 0 l 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 a - - - - D - - - 9 9 9 9 9 9 9 9 n 5 5 8 8 - 5 6 6 1 1 1 1 1 1 1 1 r B D C C X C G H D D D D D D D D e - - - - O - - - - - - - - - - - t 4 4 4 4 N 4 4 4 X X X X X X X X n 7 7 7 7 = 7 7 7 O O O O O O O O I 2 2 2 2 ( 2 2 2 N N N N N N N N . O N 1 D 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5E I 1 1 1 1 1 1LB QA E T S C C C G C G G G C C C C G G G A C C C C G G G G G A A C G G G G G G G G A C C d G G G G A A A A C d d A A A A A C C C C d A A C C C C C A d d d A C C G d A d d C A A A C G G C A C A A G C C C G C C A C G C C C G G G C A A G G C G G A C C C A G G C C A C C G A A A G C C U A G A A C G G G C U U d G C G G U C C C U d d G C U C C d U U U d G G U U d U U G G d d G U U d G G G d U U G G U d d G U U U G d d U U d G G G G d d U G G G d G G G G G G G G G G G G G G G U G G G G G G G G G U U U U G G G U U U G U U U G U U U U U U U U U G G U G U U U G G G U G U U U U G G G U U U G U U U G U U U U U U U U U G G G G U U U G G G U G G G G G G G G G G G G G G G A G G G G G G G G G A A A A G G G A A A G A A A d A A A A A A A A A G d G G A A A G G G A G d G d U G G G U U U G U U U U G U U U G G G U G G G G G G G G G G G G G G G G U G G G U U U G U U U U G U U U G G G U G G G G G G G G G G G G G G G G U G G G U U U G U U U U d U U U d d d U d d d de G G G G G G G G G G G Gc U U U U U U U U U U U Un A A A A A A A A A A A Ae G G G G G G G G G G G Gu U U U U U U U U U U U Uq C C C C C C C C C C C Ce C C C C C C C C C C C C S G G G G G G G G G G G G 7 31A A A A A A A A A A A A N N N N N N N N N N N N D D D D D D D D D D D D - - - - - - - - - - - - L L L L L L L L L L L L / / / / / / / / / / / / A A A A A A A A A A A A N N N N N N N N N N N N R R R R R R R R R R R R - - - - - - - - - - - - L L L L L L L L L L L L 0 0 4 4 - - - 0 2 2 0 4 3 3 3 - - - - 2 0 0 0 2 0 0 7 ) 3 4 4 4 3 3 3 1 A e - - - - - - - - N c 0 2 0 0 0 0 2 2 0 6 7 6 D n 4 3 4 4 3 3 3 3 3 1 1 1 x e - - - - - - - - - - - - 6r 9 0 0 2 9 9 9 0 9 9 9 9 -e 0 3 3 3 0 0 0 3 0 0 0 0 1 f D D D D D D D D D D D D 0 e - - - - - - - - - - - - 0 R 1 1 1 1 1 1 1 1 1 1 1 1 9 0 0 0 0 0 0 0 0 0 0 0 0 1l 0 0 0 0 0 0 0 0 0 0 0 0 Da 9 9 9 9 9 9 9 9 9 9 9 9 -n 1 1 1 1 1 1 1 1 1 1 1 1 X r D D D D D D D D D D D D 0 O e - - - - - - - - - - - - 4 Nt X X X X X X X X X X X X -n O O O O O O O O O O O O 2 = I N N N N N N N N N N N N 3 ( D I 6 7 8 9 0 1 2 3 4 5 6 7 1 1 1 1 2 2 2 2 2 2 2 2 Q . E O S N C G C C C C G G C G G C C A G G C A C G G C G C C A G G C A C C G A G d C A G d C A d d C C A A d C A A d C A A d d C C A d C C A d C C A A d G C A d G C A G G C C A C G C A C G C C C G G C A C G C A C G A A C C G G A C G G A C G G A A C C G A C C G A C C G G A U C G A U C G U U C C G d U C G d U C d d U U C G d U C G d U G G d d U U G d U U G d U U G G d d U G d d U G d d U U G G d U G G d U G G d d U G G d U G G d G G G G d G G G d G G G G G G G G U G G G U G G U U G G G U U G G U U G U U U U G G U U G G U U G G U U U U G U U U G U U U G G U U U G U U U G U U U U G G U U G G U U G G U U U G G U U G G U G G G G U G G G U G G G G G G G G A G G G A G G A A G G G A A G G A A G A A A A G d A A G d A A d d A A A G d A A G d A G G d d A d G d A d G d d d G G d U d G d U d G U U d d G G U d G G U d G G U U d G G U d G G U G G G G U U G G U U G G U U G G G G U G G G U G G G U U G G G U G G G U G G G G U U G G U U G G U U G G G e d U G G d U G d d U U Gc G d U G G d U G G d d Un U G d U U G d U U G G de A U G d A U G A A U U Gu G A U G G A U G G A A U 8q U G A U U G A C C G G Ae C U G A C U G C G C U G31S C C U G G G U G G G C U A A A A A A A A A A A A N N N N N N N N N N N N D D D D D D D D D D D D - - - - - - - - - - - - L L L L L L L L L L L L / / / / / / / / / / / / A A A A A A A A A A A A N N N N N N N N N N N N R R R R R R R R R R R R - - - - - - - - - - - - L L L L L L L L L L L L 7 8 9 0 1 2 3 8 9 0 1 2 0 0 0 1 1 1 1 1 1 2 2 2 e 0 0 0 0 0 0 0 0 0 0 0 0 c - - - - - - - - - - - -n A A A A A A A A A A A A e N N N N N N N N N N N N r D D D D D D D D D D D D e x x x x x x x x x x ) x x f 6 6 6 6 6 6 6 6 6 6 1 6 6 e - - - - - - - - - - 0 - - R 1 1 1 1 1 1 1 1 1 1 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0l 0 0 0 0 0 0 0 0 0 0 2 0 0a 9 9 9 9 9 9 9 9 9 9 D 9 9n 1 1 1 1 1 1 1 1 1 1 - 1 1 r D D D D D D D D D D X D D e - - - - - - - - - - O - -t X X X X X X X X X X N X Xn O O O O O O O O O O = O O I N N N N N N N N N N ( N N . O N D 8 9 0 1 2 3 4 5 6 7 8 9 I 2 2 3 3 3 3 3 3 3 3 3 3 QE S F I I A C C K H L I P P C C G G C A C A R I I G C C C C C C P T T A G d d d G C C C C G V V C A A A A C G d d C L R R d C C C C d C A A d S A A A d G G G A d C C A I V V C A C C C C A G G C R R R G C A A A G C C C G A Q E C G G G G C G A A C A E E A C C C C A C G G A R C C G A U U U G A C C G Q T T C G d d d C G U U C E E E U C G G G U C d d U C Y Y d U U U U d U G G d T K F G d d d d G d U U G E N N U G G G G U G d d U D E V d U G G G d U G G d N R R G d G G G G d G G G N A A G G U U U G G G G G V G G G G U U U G G U U G C D D U G G G G U G U U U A Y R Y R U U U U U U U G G U G C G C G G U U U U G U U U G D C L C L U G G G G U G U U U Y R K L K Q U U G G G U U G G U C G K M K V G U G G G G U G G G C L P G P P G G A A A G G G G G K Q V K V K G G A A A G G A A G K M R H S H A G d d d A G A A A V D H H H P A A G G G A A d d A V K K S K S d A d d d d A G G d S H Y E Y E G d U U U G d d d G H S K K K K d G G G G d G U U d K I A R A R U d G G G U d G G U Y N A I A I G U U U U G U G G G K A Q K Q K G G G G G G G U U G A R E D E N U G G G G U G G G U A L E A E A G U U U U G U G G G I Q V I I I 9e G G d d d G G U U G E S K T K Tc U G G G G U G d d U E A Q C Q C31n d U U U U d U G G d I V H C R Ce G d A A A G d U U G K V L E L Eu U G G G G U G A A U K C L N L Nq A U U U U A U G G A Q C Q F H Fe G A C C C G A C C G L E L A L A S C G G G G C G G G G T T D R N R A A A A A A A A A A N N N N N N N N N N D D D D D D D D D D n n n - - - - - - - - - - i i i L L L L L L L L L L e e e / / / / / / / / / / t t t A A A A A A A A A A o o o N N N N N N N N N N r r r R R R R R R R R R R p p p - - - - - - - - - - - L L L L - - L L L L L L L L L 3 4 5 6 7 8 9 0 2 3 2 2 2 2 2 2 2 3 3 3 e 0 0 0 0 0 0 0 0 0 0 c - - - - - - - - - -n A A A A A A A A A A e N N N N N N N N N N r D D D D D D D D D D e x x x x x x x x x x f 6 6 6 6 6 6 6 6 6 6 e - - - - - - - - - - R 1 1 1 1 1 1 1 1 1 1 0 0 0 0 0 0 0 0 0 0 a al 0 0 0 0 0 0 0 0 0 0 5 5a 9 9 9 9 9 9 9 9 9 9 C a Cn 1 1 1 1 1 1 1 1 1 1 5r D D D D D D D D D D n C e e - - - - - - - - - - a st X X X X X X X X X X m t un O O O O O O O O O O u a o I N N N N N N N N N N h r m D I 0 1 2 3 4 5 6 7 8 9 0 1 2 Q . 4 4 4 4 4 4 4 4 4 4 5 5 5 E O S N F L P S E L F V E T S D V Y L F S D E F A H I S P L I R V F S Q E H A T I K I A K V N K V G N L P T D T V S K A T E W K I E M T V K W A L S K S P A L P L A T V C W E G R V H F T Q H Y R E D S D V L C R L L Q L S N A G A Q F G I E L L A S R P W F H T L G T Q P L G L D E F E E D P G S V D K I T L L L N G F Q N G E G L G L E D I V R E W K T D G N T A V Q T P V S P K V L K L T I N K Y K D S E M K Y S C I F F P I I Y S P E W R D I I F Q Y I I C G R Y V S E E H A Q L F Q T K G L G I Y R C G C A S K E K T F S Y L R E M L T E C D R A G C A A R A S G K V G Q F Y E K Y P F D L F A C A C R I K T F P Y G S N I S Y F L I A L S R A C G Q E V C W V F K N D P L N S S R E T F Q C G C E P T I T L V W E A P W H C I F V A N E G C A C K D G E D P V K K N K L V D R C K Y C C A G T S A E L L V S F I G I A E M V K Y K T A G C E V V V S P V Y S L K V G E V C C K I E G C U D P C A F I S S G A V P K S A L A V Q D C U G N L I S N R M Y N T L N H T H F A F L C H U G U N L G M I Y L D D D A V K S S D G V A G N G U d V T T K N P E A L I E Y Y T S S E N E N I U G G C K N V H F A N Q K R N S K G S C E K L R G G G A M S C L E E R Y V K I V H S P V V G F V G G G G H I F G K A Y N L L D D V S I K T M I G G U U D L G Q I R S S E P A K I V S S Q I I D D U U U Y R I M E R G M V C S L D T E N I S L E Y R U G G C G G G L S K I L I V N M T E L K T Y A C G G U U C L Q S P I P S W D I L S V R Q I I Q F C L U U U K Q I T L T L L L F S S L H S L N S R E K Q U G G K M E R V G H M L A R T R V P I S V G D K L G G G V D W Y T Y T G S K F L L T K V T K K L V D G G G V K T N F I L E N R Q L Q A Y H S Y V N V K G A A S H T Y T G I K C I P A K L S G Y A L A L H A A A H S L V V R N L I G H Y V G A D F Y E L H S A G G K I S T L P I K S I T A L S C K M A A F K N G U U Y N D G H D G K N V K T L G A I T I N A Y N U G G K A P K S L E K Q T D T S F V Q C E T Q K A G G G A R L L S T Q L N F G E Y G I Y Q P C C A R G U U A L A Q S V S K Q A L V E T R D K K T S A L U G G I Q F I G G L Q E T S M T S K T D C V S I Q G G G 0e E S Q Q E S V K V L L R L V Y F P A K C E S G U Uc E A L E V Y A E Y Y A A G I D L R T K T E A U d d41n I V Q G K S S I K L Y T E L S Q H Q I T I V G G Ge K V K R Q E L L N S A G I D N D Y K F D K V U U Uu K C R V R R I P V N S T A D G V E R T R E C A A Aq Q C R V V K E D Q E I N N N Y G Y T I P Q C G G Ge L E P S C V G S G R A P I L G E V E E W L E C C C S T T V Y K G V H L A L V T L R V T A S Y M T G G G A A N N n D D i - - e L L t / / o A A r N N p R R - - - L L L n i 0 0 a 2 2 e h 0 0 c c a - -n 5 A Ae a C N N r h 0 D D e p y 2 x x f l e 0 1 2 e a k - - - R n 1 1 1 , o 0 0 0l 5 m 0 0 0 a C 9 9 9n s 1 1 1r n u D D De a s - - -t m e X X Xn u h O O O I H R N N ND I 3 4 5 6 7 Q . 5 5 5 5 5 E O S N , , , , , A A A A A d d d d d r r r r r o o o o o C C C G A A A A A G G C C C d s s s s s A d A i i i i i C A C 3 3 3 3 3 G C G n n n n n C G C A A A A A A C A C , C , C , C , C G G G G G , G A G C G C G C G C G C G C G C A d A d A d A d d U C U A d U d G r G G G G C C r C r r r G G G 5 o 5 o 5 o C o C o U U U 5 5 d d d n n n n n G G G G G G G G G 4 G4 G4 G G n s U 4 4 G G G U U U U d n s d n s d n s n s G G G G i G i G i G i d G i d U U U G 2 G 2 G G G U U U G r G r 2 r 2 r 2 r G G G K n o G n o G G n o G U n o G U n o U U U U U U U G , U U , U U , U U , U U , U G G G U U G U G U G U G U d s U d s U d U U G G G H U U s U d s d s G G G G i G i G i G i U i A A A G r G r G r G r G r A A A G o 5 G o 5 G o 5 G o 5 G G o 5 G G G R n n n n n U U U 3 U A3 U G3 U A3 U A3 U G G G n , G G G 2 U n , , , , 2 U n2 n2 n2 U U U n s s s U s U s U i d n i d n i d n i d n d G G G U U i K 1 r U 1 U r U 1 U r U 1 U r G 1 G G G n n r G o n n n 1e U U U G o G o G o G oc d d d U4G G G G n U U G n U U n U n U n1n G U G U G U G i G i G i G i ie U U U 1 e s 1 e s 1 e s 1 e G s 1 eu A A A n r sq G G G G e i n r G e i n r G e i n r G e i n r G e ie C C C U h 4 U h 4 U h 4 U h 4 U h 4 S G G G A w n A w n A w n A w n A w n A A A A A A A A N N N N N N N N D D D D D D D D - - - - - - - - L L L L L L L L / / / / / / / / A A A A A A A A N N N N N N N N R R R R R R R R - - - - - - - - L L L L L L L L 0 2 - -e 0 C C c - d ) d n A 1 1 1 e N - 0 -r D U 0 U e x d 1 d f 3 2 2 3 e - - D - R 1 1 - 1 0 0 X 0 l 0 0 O 0 a 9 9 N 9 n 1 1 = 1 r D D ( D e - - -t X X 0 X 0 n O O 2 O 2 I N N 0 N 0 D I 8 9 0 1 2 3 4 5 Q . 5 5 6 6 6 6 6 6 E O S N , , , A A A d d d r r r o o o A A A s s s i i i 3 3 3 A n A n A n C C C G , , , A A A C G G C G G G A A A A A C C C A d A d C A d A A A A C C C C C G G G G C C C C G G G G G C C C C r G r G r G G G G C C C C C A A A 5 o C5 o C5 o C C C C A A A A A G G G n A A A A G G G G G C C C G n G n G G G G G G C C C C C U U U 4 G U 4 G4 C C C C U U U U U G d d n s d n s U i d n s U U U U U G G G G d U G G G i G G i d G G G G U U U U G d U U G G G U U U U G G G d U G G d G 2 r G 2 r G 2 r G G G G G G G G G G G G G n o G n o G n o G G G G G G G G G G G G U , U U G G G G U U U G G U U G G U U G , U G , U K U U G U U U U U U U U U d s U U d s U U d s U U U U G G G U U G G U U A C G G G G U U U G G U U G G i r G i r G i r U U U U U U U U U U U U G G G H U U U G G G U U G G U G o 5 o 5 o 5 n G G G G G G G G G G G G G G G3 U G n 3 U G n 3 U G G G G G G G G G G G G n , G G G G A A 2 U n , 2 U n , A G G A A G 2 U R A A G A A A A A A A A n s s s U i d n i d n i d A A A A G G d A A G G A G G G G U d G G G U U G G 1 U r G 1 U r 1 U U U U G U U U U G G U G n o G n U n r K U G G G G G G G G G G 2e o G o G G G G U G G G G U Uc U G n U n U G n U U U U G U U U U G G U41n i U G i U G i U G G G G G G G G G G G Ge G1 e G1 e G1 e G G G G U G G G G U U Gu n r s n r s n r s U U U U d U U U U d d Uq G e i G e i G e i G G G G G G G G G G G Ge U h 4 U h 4 U h 4 U U U U U U U U U U U U S A w n A w n A w n A A A A A A A A A A A A A A A A A A A A A A A A A A A N N N N N N N N N N N N N N N D D D D D D D D D D D D D D D - - - - - - - - - - - - - - - L L L L L L L L L L L L L L L / / / / / / / / / / / / / / / A A A A A A A A A A A A A A A N N N N N N N N N N N N N N N R R R R R R R R R R R R R R R - - - - - - - - - - - - - - - L L L L L L L L L L L L L L L e c n e r e f e R l a n r e t n ID I 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0Q . 6 6 6 6 7 7 7 7 7 7 7 7 7 7 8E O S N F A R I C L C P G C C G G C C G G C G I G d C G G C C T G A G A A U G V A C C C C G A R C G d A A A A U A A C A A A C C C U G V C A C A C C G G G G U R G G G C G G C C C U d E C C C G C C A A A G G E A U A C A A G G G G G C G d G A G G C C C U U T C G C G C C U U U G G E U U U C U U d G G G G Y n G d G U d d G U U U U F i U G U d G G U G G G G N t G G d G U U d G G A A V o G G G U d d G G G A A R i G U G d G G G G G G G A B U U G G G G G U U G G G U G U G G G U G G G G D - G U U G U U U U U U U Y R U U G U U U G C U U U C G U G U U G G U G G G G C L G G U G U U U G G U U K Q G G G U U U G G G U U K V G A G U G G G G G G G P P A A G G G G G A A G G V K A d A G G G A G G G G S H G G A G A A A U U U U H P U d G A A A d U U G d K S G U U A G d G G G U G Y E G G G G d G d U U C U K K U G G U U U U G G G C A R G U U G G G G G G A - G A I G G G G G G G U U - C - A Q K - U - G - G 3e U U U U G G G G G C E N G G G U G Uc G G G G U U E C E G E A E U E d E d41n G G G G A A P A P C I I P A P G P Ge U U U U G G a C a A K T a G a U a Uu d d d d U U D A D C Q C D U D A D Aq G G G G C C k G k d R C k C k G k Ge U U U U C C 0 G 0 G L E 0 C 0 C 0 C S A A A A G G 4 C 4 C L N 4 G 4 G 4 G A A A A A A A A A N N N N N N N N N D D D D D D n D D D - - - - - - i - - - L L L L L L e L L L / / / / / / t / / / A A A A A A A A o A A A N N N N N N N N r N N N R R R R R R R R p R R R - - - - - - - - - - - - L L L L D D L L D L L L - - d D 0 e - - 2 - - re e a 0 X C = rc s D - O d ( en u k A N 1 fe o 0 ) N - G e r m 4 9 D = U E r )e ’ 1 x ( d P 1f d 5 D 6 2 - o 2e e - - - G - a s D R 2 2 9 1 t 1 X 1 E 1 D l - 0 0 1 2 a 0 O 0 P 0 k a Nl 0 0 D D l 0 N 0 - 0 0 O a - - - - y 9 9 a 9 4 1 An 6 5 X X n 1 = 1 D 1 ’ 2r H D O O i D ( D k D 5 D s e - - N N t - - 0 ) - - - at 4 4 v v o a X G X 4 0 X 0 Xn 7 7 e e i 5 O E O ’ 2 O 2 O o I 2 2 r r B C N P N 5 D N 0 N t D I 1 2 3 4 5 6 7 8 9 0 1 2 Q . 8 8 8 8 8 8 8 8 8 9 9 9 E O S N F I A C K L I P C G R I P T G V L R S A I V R R A E A E R C Q T E E C Y T F a E N c D V N R a N A a V G c C D A Y c G C G c D C L a Y K Q C G K V c C L P P a K Q V K g K M S H V D H P c V K K S t S H Y E g H S K K K I A R c Y N A I g K A Q K t A R E N - A L E A O I Q I I O 4e E S K T -c E A Q C 541n I V R C 2 e K V L E 4 u K C L N o q Q C H F t e L E L A t S T T N R A n n i i e e t t o o r r p p A - N L -L P e c n a a e 5 5 r C C e g g;2f r r e A A0- R - -12s s l e eD-a d d N n O r n e e a sA-t m u A n u o I h m N P D I 3 4 5 Q . 9 9 9 E O S N The present invention is further illustrated by the figures, examples and the sequence listing from which further features, embodiments and advantages may be taken, wherein Fig.1 shows an alignment of sequences of nucleic acid molecules capable of binding human and mouse C5a including the KD value and relative bindingactivity to human and mouse C5a as determined by suface plasmonresonance measurement; the nucleic acids were tested as Spiegelmers (L- nucleic acids) also referred to as L-aptamers; Figs.2 shows derivatives of nucleic acid molecule NOX-D19001 with a single ribonucleotide to 2’-deoxyribonucleotide substitution including the KDvalue and relative binding activity to human C5a as determined by sufaceplasmon resonance measurement, the nucleic acids were tested as Spiegelmers (L-nucleic acids) also referred to as L-aptamers; Figs.3 shows derivatives of nucleic acid molecule NOX-D19001 with two, three, four, five or six ribonucleotide to 2’-deoxyribonucleotide substitutions including the KD value and relative binding activity to human C5a asdetermined by suface plasmon resonance measurement, the nucleic acids were tested as Spiegelmers (L-nucleic acids...

Claims

Claims1. A C5a binding agent for use in a method for treating and / or preventing a disease in asubject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering to the subject several individual doses Df of the C5a binding agent, wherein a doseDf of the several individual doses Df, preferably each of the several individual doses Df, is asfollows:Df = Dose x (1 ± v), wherein(Formula I) wherein Df = dose to be administered (nmol / kg body weight of the subject),I = dosing interval (h),Ctrough = target level of the C5a binding agent in blood of the subject (nmol / L) at steady state,0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject.

2. The C5a binding agent for use of claim 1, wherein Ctrough is from about 80 nmol / L to about300 nmol / L.

3. The C5a binding agent for use of any one of claims 1 to 2, wherein Ctrough is from about 80nmol / L to about 150 nmol / L, preferably Ctrough is about 100 nmol / L.

4. The C5a binding agent for use of any one of claims 1 to 3, wherein the dosing interval I isfrom about 1 hours to about 96 hours, preferably the dosing interval I is from about 4 hours to about 72 hours, more preferably the dosing interval I is from about 6 hours to about 60 hours, most preferably the dosing interval I is from about 8 to about 48 hours.

5. The C5a binding agent for use of any one of claims 1 to 4, wherein in Formula IDf = Dose x (1 ± v),0 ≤ v ≤ 0.1, preferably 0 ≤ v ≤ 0.05.

6. The C5a binding agent for use of any one of claims 1 to 5, wherein the C5a binding agenthas an initial elimination half-life t1 / 2 within the first 8 to 96 hours after administration to a subject of about 5 hours to about 15 hours, preferably the C5a binding agent has an initial elimination half-life t1 / 2 within the first 12 to 48 hours after administration to a subject of about 5 hours to about15 hours, more preferably about 5 hours to about 12 hours.

7. The C5a binding agent for use of any one of claims 1 to 6, wherein the affinity of the C5abinding agent for C5a is about ≤ 30 nmol / L, preferably about ≤ 8 nmol / L.

8. The C5a binding agent for use of any one of claims 1 to 7, wherein the method comprisesadministering an amount of 4 to 210 nmol of the C5a binding agent per kg body weight of the subject to the subject over a period of 8 to 48 hours.

9. The C5a binding agent for use of any one of claims 1 to 8, wherein the method comprisesadministering the C5a binding agent to the subject as follows, a) 95 to 210 nmol of the C5a binding agent per kg body weight of the subject every two days,b) 25 to 60 nmol of the C5a binding agent per kg body weight of the subject every day,c) 8 to 23 nmol of the C5a binding agent per kg body weight of the subject twice a day, ord) 4 to 15 nmol of the C5a binding agent per kg body weight of the subject three times a day.

10. A C5a binding agent for use in a method for treating and / or preventing a disease in asubject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering to the subject several individual doses Di of the C5a binding agent, wherein a dose Di of the several individual doses Di, preferably each of the several individual doses Di is as follows:Di = Dose x (1 ± v), whereinnmol⁄ kg^^^^ = ^0.0713 ∙ ^^^^^^^ − 0.0156 nmol⁄ ^(Formula II) wherein Di = dose to be administered (nmol / kg body weight of the subject),I = dosing interval (h),Ctrough = target level of the C5a binding agent in blood of the subject (nmol / L) afterthe first dose of the C5a binding agent has been administered to the subject, 0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject or wherein the method comprises administering to the subject only a single dose Ds, the single dose Ds is calculated as follows:Ds = Dose x (1 ± v), wherein^^^^ = ^0.0713+∙ nmol⁄ kg ∙ ^ ^nmol⁄ L h ^ ∙ ^(Formula III) whereinDs = single dose of the C5a binding agent to be administered (nmol / kg body weight ofthe subject),I = Interval from dosing for which inhibition of elevated C5a shall be present (h),Cmin = minimal concentration of the C5a binding agent in blood of the subject (nmol / L)required for inhibition at the Interval I after Ds has been administered to the subject,0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject.

11. The C5a binding agent for use of claims 10, wherein Ctrough and Cmin are each andindividually from about 80 nmol / L to about 300 nmol / L.

12. The C5a binding agent for use of any one of claims 10 to 11, wherein Ctrough and Cmin areeach and individually is from about 80 nmol / L to about 150 nmol / L, preferably Ctrough is about 100nmol / L.

13. The C5a binding agent for use of any one of claims 10 to 12, wherein the dosing interval Iis from about 1 hours to about 96 hours, preferably the dosing interval I is from about 4 hours toabout 72 hours, more preferably the dosing interval I is from about 6 hours to about 60 hours, andmost preferably the dosing interval I is from about 8 to about 48 hours.

14. The C5a binding agent for use of any one of claims 10 to 13, wherein the C5a binding agenthas an initial elimination half-life t1 / 2 within the first 8 to 96 hours after administration to a subject of about 5 hours to about 15 hours, preferably the C5a binding agent has an initial elimination half- life t1 / 2within the first 12 to 48 hours after administration to a subject of about 5 hours to about15 hours, more preferably about 5 hours to about 12 hours.

15. The C5a binding agent for use of any one of claims 10 to 14, wherein the affinity of theC5a binding agent for C5a is about ≤ 30 nmol / L, preferably about ≤ 8 nmol / L.

16. The C5a binding agent for use of any one of claims 10 to 15, wherein the method comprisesadministering an amount of 7 to 225 nmol of the C5a binding agent per kg body weight of the subject to the subject over a period of 8 to 48 hours.

17. The C5a binding agent for use of any one of claims 10 to 16, wherein the methodcomprises administering the C5a binding agent to the subject, a) 100 to 225 nmol of the C5a binding agent per kg body weight of the subject every twodays, b) 29 to 75 nmol of the C5a binding agent per kg body weight of the subject every day,c) 12 to 36 nmol of the C5a binding agent per kg body weight of the subject twice a day, ord) 7 to 25 nmol of the C5a binding agent per kg body weight of the subject three times a day.

18. A C5a binding agent for use in a method for treating and / or preventing a disease in asubject, wherein the disease is associated with or caused by C5a, wherein the method comprises, after administration of a loading dose of the C5a binding agent to the subject, continuously administering the C5a binding agent to the subject, wherein a dose for continuous administration Dca isDca = DoseContInf x (1 ± v), wherein^^^^ nmol⁄kg∙hnmol ^^^^^^^ = ^. ^^^⁄∙ ^^^^^^^nmol L + ^. ^^^kg h (Formula IV),wherein DoseContInf = Continuous infusion dose per hour (nmol / kg (body weight of the subject)∙h),Ctarget = target level of the C5a binding agent in blood of the subject (nmol / L) that is or is tobe constant over the duration of the continuous administration, 0 ≤ v ≤ 0.2, and kg in the above formula refers to kg body weight of the subject.

19. The C5a binding agent for use of claim 18, wherein Ctarget is from about 80 nmol / L to about300 nmol / L.

20. The C5a binding agent for use of any one of claims 18 to 19, wherein Ctarget is from about80 nmol / L to about 150 nmol / L, preferably Ctargetis about 100 nmol / L.

21. The C5a binding agent for use of any one of claims 18 to 20, wherein the C5a binding agenthas an initial elimination half-life t1 / 2 within the first 8 to 96 hours after administration to a subjectof about 5 hours to about 15 hours, preferably the C5a binding agent has an initial elimination half- life t1 / 2 within the first 12 to 48 hours after administration to a subject of about 5 hours to about15 hours, more preferably about 5 hours to about 12 hours.

22. The C5a binding agent for use of any one of claims 18 to 21, wherein the affinity of theC5a binding agent for C5a is about ≤ 30 nmol / L, preferably about ≤ 8 nmol / L.

23. The C5a binding agent for use of any one of claims 18 to 22, wherein the loading doseDoseload = Ctarget / DNCmax, wherein DNCmax is the dose-normalized Cmax calculated as Cmax divided by the applied dose of the C5a binding agent, preferably DNCmax is from about 15 (nmol / L) / (nmol / kg body weight of the subject) to about 32 (nmol / L) / (nmol / kg body weight of the subject), more preferablyDNCmax is from about 15.7 (nmol / L) / (nmol / kg body weight of the subject) to about 31.2 (nmol / L) / (nmol / kg body weight of the subject).

24. The C5a binding agent for use of claim 23, wherein DNCmax is from about23(nmol / L) / (nmol / kg body weight of the subject) to about 24 (nmol / L) / (nmol / kg body weight ofthe subject), preferably about 23.4 (nmol / L) / (nmol / kg body weight of the subject).

25. The C5a binding agent for use of any one of claims 18 to 24, wherein the method comprisesadministering to the subject a loading dose of 3 to 13 nmol of the C5a binding agent per kg body weight of the subject.

26. The C5a binding agent for use of any one of claims 18 to 25, wherein the method comprises,after administering the loading dose to the subject, administering to the subject a continuous infusion of 0.4 to 1.4 nmol of the C5a binding agent per kg body weight of the subject per hour.

27. A C5a binding agent for use in a method for treating and / or preventing a disease in asubject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering the C5a binding agent to the subject as follows: a) 95 to 225 nmol of the C5a binding agent per kg body weight of the subject every two days,b) 25 to 75 nmol of the C5a binding agent per kg body weight of the subject every day,c) 8 to 36 nmol of the C5a binding agent per kg body weight of the subject twice a day, ord) 4 to 25 nmol of the C5a binding agent per kg body weight of the subject three times a day.

28. The C5a binding agent for use of claim 27, wherein a dose of 15.19 nmol of the C5abinding agent per kg body weight of the subject is administered to the subject every 11 to 13 hours, preferably every 12 hours.

29. The C5a binding agent for use of any one of claims 27 to 28, wherein the C5a binding agentis AON-D21 comprises a nucleotide sequence according to SEQ ID NO: 92 and is represented bythe following structural formula:(structural formula I)wherein NHC6H12O is a hexylamino linker and R isand n is approximately 450, wherein the molecular formula is C398H458N160Na40O287P40[C2H4O]2n, wherein n is approximately 450.

30. A C5a binding agent for use in a method of treating a disease in a subject, wherein thedisease is associated with or caused by C5a, wherein the subject is suffering from the disease, and wherein the subject has an elevated C5a activity in the blood, wherein the method comprises administering to the subject a dose of the C5a-binding agent, wherein the C5a binding agent administered to the subject inhibits the elevated C5a activity in the blood of the subject to a healthy-state level or below a healthy-state level, wherein the inhibition of the elevated C5a activity is, after a last administration of the C5a bindingagent to the subject, effective for 0 hours to 96 hours, preferably for 0 hours to 72 hours.

31. The C5a binding agent for use of claims 30, wherein a level of the C5a binding agent inthe blood of the subject of ≥ about 100 nM is effective in inhibiting the elevated C5a activity inthe blood of the subject, preferably the elevated C5a activity is inhibited by at least 80 %, preferably at least 90 % and more preferably 100 %.

32. The C5a binding agent for use of claim 31, wherein the level of the C5a binding agent isbelow about 50 nM within about 5 to about 15 hours after the level of the C5a binding agent in theblood of the subject is lower than the level effective in inhibiting the elevated C5a activity in theblood of the subject, preferably the inhibition of the elevated C5a activity is 50 % or less, preferably compared to the maximum inhibition realized in the administration of the C5a binding agent.

33. The C5a binding agent for use of any one of claims 31 to 32, wherein the level of the C5abinding agent is below about 10 nM in the period of 17 hours to 48 hours, preferably the inhibitionof the elevated C5a activity is 10 % or less, preferably compared to the maximum inhibition realized in the administration of the C5a binding agent.

34. The C5a binding agent for use of any one of claims 30 to 33, wherein the elevated level of C5a activity is a level of C5a activity associated with or caused by the disease.

35. The C5a binding agent for use of any one of claims 30 to 34, wherein the elevated levelof C5a activity is a C5a level in the blood of the subject of > 3nM, preferably ≥ 5.2 nM.

36. The C5a binding agent for use of claim of any one of claims 30 to 35, wherein the levelof C5a activity in a state of health is a level of C5a in blood which is characteristic for subjects not suffering from the disease, preferably the level of C5a activity in a state of health is a level of C5a in blood of a subject ≤ 3 nM.

37. A C5a binding agent for use in a method for treating and / or preventing a disease in asubject, wherein the disease is associated with or caused by C5a, wherein the method comprises administering the C5a binding agent to the subject, wherein the method reduces treatment- emergent adverse events (TEAEs) or reduces the risk of treatment-emergent adverse events (TEAEs), wherein the C5a binding agent is AON-D21 comprises a nucleotide sequence accordingto SEQ ID NO: 92 and is represented by the following structural formula:(structural formula I)wherein NHC6H12O is a hexylamino linker and R isand n is approximately 450, wherein the molecular formula is C398H458N160Na40O287P40[C2H4O]2n, wherein n is approximately 450.

38. A C5a binding agent for use in a method for treating and / or preventing a disease in asubject, wherein the disease is associated with or caused by C5a, wherein the method comprisesadministering the C5a binding agent to the subject, wherein the method reduces treatment-emergent adverse events (TEAEs) or reduces the risk of treatment-emergent adverse events (TEAEs), wherein the C5a binding agent has an initial elimination half-life t1 / 2within the first 8 to 96 hours after administration to a subject of about 5 hours to about 15 hours, preferably the C5a binding agent has an an initial elimination half-life t1 / 2 in the first 12 to 48 hours after administration to a subject of about 5 hours to 15 hours, more preferably about 5 hours to about 12 hours.

39. The C5a binding agent for use of claim 38, wherein the affinity of the C5a binding agentfor C5a is about ≤ 30 nmol / L, preferably about ≤ 8 nmol / L.

40. A packaging comprising a C5a binding agent, wherein the packaging comprises apharmaceutical composition of the C5a binding agent and information on the use of the pharmaceutical composition, wherein the information comprises dosage or dose of the C5a bindingagent, wherein the dosage is as defined in any one of claims 1 to 29, preferably the pharmaceuticalcomposition is present as a unit dose.

41. The packaging of claim 40, wherein the unit dose is suitable for adjustment to subject-specific administration.

42. The packaging of any one of claims 40 to 41, wherein the information is provided by ameans selected from the group comprising a package insert, a bar code, a QR code or any link toa database or server providing the information.

43. The C5a binding agent for use of any of claims 1 to 39 and the packaging of any one ofclaims 40 to 42, wherein the C5a binding agent is capable of binding to C5a and C5, preferably the C5a binding agent is an agent having a binding affinity to C5a with a KDof about 0.1 to 5 nM, more preferably of 0.1 to 2 nM, most preferably of 0.1 to 1.0 nM, and / or preferably the C5a binding agent has a binding affinity to C5 with a KD of about 0.1 to 5 nM, preferably 0.1 to 2 nM, more preferably 0.1 to 1.0 nM.

44. The C5a binding agent for use of any one of claims 1 to 43 and the packaging of any oneof claims 40 to 43, wherein the C5a binding agent is a C5a binding L-nucleic acid molecule, optionally comprising a modification, wherein the L-nucleic acid molecule comprises a central stretch of nucleotides, wherein the central stretch of nucleotides comprises a nucleotide sequence of5’ AUGn1GGUGKUn2n3RGGGHUGUKGGGn4Gn5CGACGCA 3’ [SEQ ID NO: 61], whereinn1 is U or dU, n2 is G or dG, n3 is A or dA, n4 is U or dU, n5 is U or dU andG, A, U, C, H, K, and R are ribonucleotides, and dU, dG and dA are 2’-deoxyribonucleotides.

45. The C5a binding agent for use of claim 44 and the packaging of claim 44, wherein theC5a binding agent is compound AON-D21 comprises a nucleotide sequence according to SEQID NO: 92 and is represented by the following structural formula:(structural formula I)wherein NHC6H12O is a hexylamino linker and R isand n is approximately 450, wherein the molecular formula is C398H458N160Na40O287P40[C2H4O]2n, wherein n is approximately 450.

46. The C5a binding agent for use of any one of claims 1 to 40 and 43 to 45, whereinadministering the C5a binding agent to the subject comprises administering the C5a binding agent to the subject by intravenous administration, subcutaneous administration or administration byinhalation, wherein preferably administering the C5a binding agent is administering the C5a binding agent by intravenous administration.

47. The C5a binding agent for use of any one of claims 1 to 40 and 43 to 46, wherein thedisease associated with or caused by C5a is a disease selected from the group comprising a disease associated with complement activation and C5a-mediated pathogenic mechanisms, and / or is selected from the group comprising an autoimmune disease, an inflammatory disease, a systemic inflammatory response syndrome, a disease of the eye, an ischemia / reperfusion injuries, a delayed graft function, a transplant rejection, a cardiovascular disease, a respiratory disease, an acute reactions, an infectious disease, a neurological disease, a neurodegenerative disease, a fibrotic disease, a hematological disease, a metabolic disease, a tumor and a clinical complication associated with complement activation by biomaterials, wherein preferably the systemic inflammatory response syndrome is selected from the group comprising sepsis and a secondary damage of trauma or a severe burn; the tumor is cancer, more preferably lung cancer; and the respiratory disease is pneumonia.

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