WO2024028192A1

WO2024028192A1 - Use of conjugates of human serum albumin and phosphocholine for blocking c-reactive protein

Info

Publication number: WO2024028192A1
Application number: PCT/EP2023/070776
Authority: WO
Inventors: Ahmed Sheriff; Birgit Vogt; Rudolf Kunze
Original assignee: Pentracor Gmbh
Priority date: 2022-08-04
Filing date: 2023-07-26
Publication date: 2024-02-08

Abstract

The present invention relates to CRP-binding phosphocholine-HSA conjugates and their use for binding and/or neutralizing CRP in the blood flow. The phosphocholine-HSA conjugates according to the invention are specifically useful in the treatment and/or prevention of acute or chronic diseases associated with elevated CRP levels and/or caused by elevated CRP levels.

Description

Use of phosphocholine-human serum albumin conjugates for blocking C-reactive protein The present invention relates to CRP-binding phosphocholine-human serum albumin conjugates and their use for binding and/or neutralizing CRP in the bloodstream. The phosphocholine-HSA conjugates according to the invention are particularly useful for the treatment and/or prevention of acute or chronic diseases that are associated with and/or caused by an increased CRP level. In human medicine, C-reactive protein (CRP) has been known as the acute phase protein for many years. Elevated CRP blood levels are particularly observed in inflammations of various causes. CRP is therefore one of the most important indicators of inflammatory disease processes. The production of CRP takes place in the liver. Its synthesis is triggered by an injury and/or infection hours later and for a limited time. CRP formation depends on stimulation by proinflammatory cytokines, especially by interleukin-6. CRP is a phylogenetically ancient molecule and widespread in the animal kingdom. It was first discovered in 1930 in the blood of people with acute bacterial infections. The physiologically dominant form is a pentamer made up of identical subunits that are not covalently linked. With a molecular weight of approximately 125,000 Da, it is one of the larger plasma molecules. Concentrations of 0.2-3 mg/L blood are considered the normal range. In the local microenvironment, in the presence of low pH and oxidative stress species (ROX), CRP undergoes a conformational change that allows complement binding (C1q), as well as the dissociation of the pentameric form (pCRP) into its monomers (mCRP). Both enable or increase local inflammatory processes. The dissociation of the pentamer is a localized event, which is said to be promoted by lyso-phosphocholine. The monomeric CRP is said to play a special role in destroying the blood-retinal barrier (Mollins et al. Front. Immunol.2018, 9:808). According to the authors, moderately elevated pCRP levels are in balance with the locally pathologically more active mCRP. In an animal model (rat, ischemia model).

PEN-P04423WO07 Patent application (final).docx by Braig et al. (Nat Commun; 2017, 8: 14188) and Thiele et al. (Front Immunol; 2018, 9: art.6) showed that in capillary vessels of muscle tissue, leukocyte rolling and adherence are increased by mCRP, but not by pCRP. The local molecular inflammatory cascade is probably enhanced with the formation of mCRP. The authors assume that the conformational change of CRP is the key to understanding vascular inflammatory pathomechanisms, representative of diseases whose triggers are vascular narrowing or occlusion (e.g. heart attack, stroke). CRP is one of the few plasma molecules whose concentration can increase more than a hundredfold. This is triggered by vascular occlusions such as a heart attack or stroke, but also by an acute infection, sepsis, burn injury, severe trauma, acute pancreatitis or operations. The CRP concentration increases after one of the above-mentioned events with a delay of several hours. For example, a peak is observed around 48 hours after a heart attack, while in the days afterwards the CRP level drops continuously. The individual CRP responder rate, extent and duration vary greatly. Independently of each other, the research groups led by Lucchesi (Barrett et al, J Pharmacol Exp Ther 2002;303(3):1007-1013) and Pepys (Griselli et al, J Exp Med 1999;190(12):1733-1740; Gill et al, J Cereb Blood Flow Metab 2004;24(11):1214-1218) showed a proedematous and pronecrotic effect of CRP in heart attacks and strokes in rabbits and rats. From an evolutionary perspective, in addition to a certain antibacterial effect, the function of CRP is to mark necrotic and pronecrotic cells in order to then dispose of them with the help of complement proteins and phagocytes and initiate tissue regeneration. This mechanism is essential for the healing of external wounds, but for the healing of internal, aseptic wounds such as heart attacks or strokes, excessive CRP concentrations may be counterproductive. In other words, evolution is not prepared for this type of injury or wound. The molecular mechanisms of the proinflammatory effect of CRP on the cell surface are broadly known. In the event of a local injury, acute inflammation follows. Three cell populations can temporarily arise at the cellular level: vital, reversibly defective and irreversibly defective cells. The transitions between the latter two are fluid. CRP is a trigger of the

PEN-P04423WO07 Patent application (final).docx Cell death or necrosis, and it probably depends on the amount of CRP on site how high the proportion of reversibly damaged cells is that reaches the “point of no return”. The natural ligand of CRP, lyso-phosphatidylcholine (LPC), is practically not present in vital cells as a component of the cell membrane. However, if cell damage occurs, LPC is produced on the cell surface by a special phospholipase, another acute phase protein. This is the secretory phospholipase A2 type IIa (sPLA2 IIa). The more CRP there is, the more CRP molecules bind to the newly formed LPC molecules. Cells in an infarct area are usually poorly supplied with oxygen and nutrients and therefore switch their metabolism from the respiratory chain to glycolysis, which leads to a depletion of energy equivalents. Otherwise, the newly created LPC would be repaired immediately. When CRP binds to the pronecrotic cell or LPC, it undergoes a conformational change and the inflammatory cascade is initiated, which now enables the complement protein C1q to bind to CRP. The complement cascade then runs up to C4 and factor H. The result is the invasion of monocytes and the induction of proinflammatory cytokines, which in turn stimulate the synthesis of CRP in the liver. The “clearing” of dead or no longer fully functional cells, e.g. by phagocytes, is an essential mechanism for initiating tissue regeneration and wound healing. The normal value for CRP in the blood of people varies from person to person, with the median being around 0.8 mg CRP per liter of blood, but can be significantly higher in the case of acute or chronic inflammatory reactions (e.g. bacterial infections, or after a heart attack). 100 mg of CRP per liter of blood increases. Since the half-life of CRP in the blood (approx. 19 hours) is constant and therefore independent of the patient's health condition, only the synthesis rate of CRP is responsible for the regulation of the CRP level in the blood (Pepys & Hirschfield, J. Clin. Invest ., 2003, 111: 1805-1812). The greatly increased synthesis of CRP in acute pathological conditions therefore places special demands on therapeutic approaches to CRP removal from patients (at-risk patients or acute patients), since a significant amount of CRP must be removed in order to bring the CRP level in the blood to normal values to lower. Damage to the heart after a heart attack or to the brain after a stroke is increased by CRP and subsequent complement effects.

PEN-P04423WO07 Patent application (final).docx Essentially, three ways of reversing the effect of CRP are known: • the inhibition of CRP synthesis • the elimination of CRP from the bloodstream • the pharmacological blockade of CRP An effective inhibition of CRP synthesis is possible with the help of antisense oligonucleotides, which inhibit CRP synthesis in the liver (Noveck et al J Am Heart Assoc. 2014; doi.org/10.1161/JAHA.114001084). This was shown in healthy subjects who had high plasma levels of CRP after an injection of endotoxin. However, the drug ISIS-CRPRx was preadministered in 6 doses over 22 days. Obviously, the oligonucleotide is not suitable for lowering acute CRP concentrations, such as those that can occur in the event of a heart attack or stroke. CRP can be eliminated from the bloodstream or blood plasma using selective apheresis using a CRP adsorber. The practicality and efficiency of a CRP apheresis system for acute inflammation has previously been demonstrated in a porcine infarction model (Sheriff et al., Journal of Clinical Apheresis 2015; 30: 15-21. doi.org/10.1002/jca.21344). Using a CRP adsorber, the amount of CRP in the animals' blood was reduced after the infarction had been triggered. The subsequent cardiac examination using MRI and histology revealed a significantly smaller infarct area and less scar tissue in the treatment group compared to the control animals. Previous findings from a pilot study on patients with heart attacks confirmed the positive effect of CRP apheresis (Ries et al. C-reactive protein apheresis as anti-inflammatory therapy in acute myocardial infarction: Results of the CAMI-1 study. Front Cardiovasc Med 2021; 8 :591741). The infarct area is significantly smaller in patients with CRP apheresis. With the reduction of the CRP concentration in the blood, the amount of CRP on ischemic or pronecrotic cells, for example in an infarct area, is probably reduced, with the result that fewer binding sites are available for complement proteins. The part of the affected inflammatory tissue that has only been previously damaged but is reversible is able to regenerate. Whether this regenerative process occurs through lowering the CRP concentration in tissues other than muscle cells is unknown, but likely. The specific CRP adsorber can in principle be used as a medical product where, in the course of a preferably acute inflammation or illness with high CRP levels.

PEN-P04423WO07 Patent application (final).docx Reflect elimination of CRP is of therapeutic benefit. However, due to the medical technology requirements, the procedure cannot always be used where the reduction of functionally active CRP or CRP blood levels is desired. The use of extracorporeal apheresis procedures such as CRP apheresis, immunoadsorption or lipid apheresis requires considerable medical technology effort. This represents a certain technical limitation in the practicability of the process. Pharmacological blockade of CRP is the third therapeutic option to limit the effects of CRP on previously damaged cells or tissues, as is known from heart attacks or strokes. The active ingredient 1,6-bis(phosphocholine)-hexane blocks CRP in vivo. Using the active ingredient derived from the natural ligand phosphocholine, an experiment on rats demonstrated that blocking CRP leads to a reduced volume of the artificially induced heart attack (Pepys et al, Nature 2006; 440(7088):1217-1221) . However, to be effective, the CRP blocker was administered before the heart attack occurred and not immediately afterwards. For the acute treatment of a heart attack, the active ingredient should take effect immediately or at least within a few minutes. An active ingredient/drug that directly has CRP as a therapeutic target is currently not available. US patent application US 2016/0131661 A1 describes phosphocholine conjugates for the treatment and prevention of atherosclerosis and for the detection of anti-phosphocholine antibodies (IgM), which are associated with cardiovascular diseases. The conjugates contain snail hemocyanin (KLH), bovine serum albumin (BSA) or HSA carrier proteins and are used to bind to IgM antibodies. A connection between the CRP level, the anti-phosphocholine antibodies or the intima-media thickness, which is used to determine the progression of atherosclerosis, could not be observed in the experimental examples. The object of the present invention is therefore to provide a medicament for binding and/or neutralizing CRP in vivo, especially in the bloodstream, in particular for the treatment and/or prevention of acute or chronic diseases that are associated with an increased CRP level and/ or caused. This object is solved by the technical teaching of the independent claims of the present invention. Further advantageous embodiments of the invention

PEN-P04423WO07 Patent application (final).docx result from the dependent claims, the description and the examples. The inventor has surprisingly found that a C-reactive protein-binding phosphocholine conjugate or a pharmaceutical composition thereof is suitable for binding and/or neutralizing C-reactive protein in the blood, the C-reactive protein-binding phosphocholine conjugate being covalently attached Human serum albumin-bound phosphocholine or phosphocholine derivative includes. The said conjugate or a pharmaceutical formulation thereof is therefore particularly suitable for the treatment and/or prevention of acute or chronic diseases that are associated with and/or caused by an increased CRP level. Brief description The present invention relates to a C-reactive protein-binding phosphocholine conjugate or a pharmaceutical composition thereof for use as a medicament for binding and/or neutralizing C-reactive protein in the blood, wherein the C-reactive protein-binding phosphocholine conjugate is a human - serum albumin (HSA) includes covalently bound 4-aminophenylphosphocholine (APPC). The inventor has discovered that CRP-binding APPC-HSA conjugates of the present invention efficiently bind CRP in biological fluids and are therefore particularly suitable for the treatment of diseases associated with and/or caused by elevated CRP levels. In particular, the APPC-HSA conjugates described herein are suitable for the treatment and/or prevention of diseases caused by and/or associated with a C-reactive protein blood level of >>5 mg/L. A particular advantage of the CRP-binding APPC conjugate according to the invention is its rapid distribution in the bloodstream and in the interstitial spaces, which makes the said conjugate particularly suitable for the acute treatment of diseases such as infarctions or strokes. The APPC-HSA conjugates of the present invention comprise a 4-aminophenyl-phosphocholine that binds to CRP under physiological conditions so that the

PEN-P04423WO07 Patent application (final).docx Concentration of free CRP in the bloodstream decreases. Preferably, the APPC-HSA conjugates of the present invention bind monomeric CRP and/or pentameric CRP. The APPC-HSA conjugates according to the invention have the structure of the general formula (I):

where L represents a bond or linker; m comprises a number between 1 and 100; and HSA stands for human serum albumin. A further aspect of the present invention relates to a pharmaceutical composition comprising the APPC-HSA conjugate according to the invention, a pharmaceutically acceptable carrier, an excipient and/or a diluent. In a further embodiment, the APPC-HSA conjugate according to the invention or the pharmaceutical composition thereof can be used in combination with extracorporeal methods for lowering CRP levels, such as dialysis or apheresis. In a further embodiment, the APPC-HSA conjugate according to the invention or the pharmaceutical composition thereof can be used in combination with at least one complement blocker for the treatment of diseases associated and/or caused by an increased CRP level. Description of the Invention Definitions: The term "linker" as used herein includes molecular fragments capable of linking the 4-aminophenylphosphocholine at the aromatic amino group to the human serum albumin as a carrier molecule. More accurate

PEN-P04423WO07 Patent application (final).docx said, the linker connects the 4-aminophenylphosphocholine to the human serum albumin in such a way that the phosphocholine group is terminal and is therefore able to bind the CRP. Thus, the function of the linker is to create, maintain and/or bridge a specific distance between the phosphocholine and the HSA carrier molecule. The term "human serum albumin" or "HSA" or "human albumin" as used herein includes the human form of the globular blood protein albumin. The human serum albumin used in the conjugates of the present invention may be of natural origin or synthetically produced. The term "physiological conditions" as used herein refers to a temperature, a pH, an osmotic pressure, an osmolality, oxidative stress, an electrolyte concentration, a concentration of a small organic molecule such as glucose, lactic acid, pyruvate, Nutrient components, other metabolites and the like, a concentration of another molecule such as oxygen, carbonate, phosphate and carbon dioxide, and cell types and nutrient availability considered to be within a normal range at the site of administration or at the tissue or organ at the site of effect on a subject would. The physiological conditions preferably relate to the conditions prevailing in the human organism at a temperature of 37 ° C, including pathophysiological conditions such as fever (temperature 37.5 ° C - 42 ° C), a pH value of 7.4, including a local one Variation from 5.0 to 8.5, such as in a wound or disease, and an osmotic pressure of approximately 300 mosmol/kg. The term "biological fluid" as used herein refers to aqueous solutions occurring in mammals, and preferably humans, containing CRP, such as cerebrospinal fluid, peritoneal fluid, pleural fluid, ascitic fluid, blood, blood plasma, liver extracts, and Interstitial fluid. The term "CRP-binding" as used herein means that the APPC-HSA conjugates described herein are capable of reacting with and/or binding to C-reactive protein via their terminal phosphocholine group and /or to form a complex with the CRP.

PEN-P04423WO07 Patent application (final).docx The term "neutralization" as used herein refers to the prevention of the proinflammatory effects of CRP as well as activation of the complement system and/or interaction with immunocompetent cells. Neutralization can thus be achieved by suppressing the binding of CRP to phosphocholine and/or phospholipid components of destroyed endogenous cells, or by preventing complement activation, or by preventing binding to phagocytes. The term "complement blocker" or "complement inhibitor" as used herein refers to drugs that reduce and/or inhibit the activity of individual components of the complement system or the entire complement system. Complement blockers or complement inhibitors therefore bind to plasma proteins, such as the C3 and/or the C5 plasma protein, at molecularly defined locations and thus prevent complement activation. The term "postoperative condition" as used herein refers to the condition of a patient following a surgical procedure (invasive intervention into the patient's body performed by a surgeon), including vasoconstrictions, thromboembolic diseases and sequelae of muscular and musculoskeletal injuries . The present invention relates to a C-reactive protein-binding phosphocholine conjugate or a pharmaceutical composition thereof for use as a medicament for binding and/or neutralizing C-reactive protein in the blood, the C-reactive protein-binding phosphocholine conjugate being bound to human serum albumin covalently bound 4-aminophenylphosphocholine. The 4-aminophenylphosphocholine is covalently bound to the human serum albumin in such a way that a terminal phosphocholine group is formed with the structure shown below, where the dashed line represents the covalent bond to the HSA.

Preferably, the 4-aminophenylphosphocholine is attached to a carboxylic acid group of a side chain of an amino acid, glutamic acid or aspartic acid, of HSA

PEN-P04423WO07 Patent application (final).docx bound. Thus, the present invention relates to a C-reactive protein-binding phosphocholine conjugate or a pharmaceutical composition thereof for use as a medicament for binding and/or neutralizing C-reactive protein in the blood, wherein the C-reactive protein-binding phosphocholine conjugate is a Carboxylic acid residue of human serum albumin comprises covalently bound 4-aminophenylphosphocholine. The 4-aminophenylphosphocholine can be bound to the HSA either directly or via a linker. The present invention therefore also relates to a C-reactive protein-binding phosphocholine conjugate or a pharmaceutical composition thereof for use as a medication for binding and/or neutralizing C-reactive protein in the blood, wherein the C-reactive protein-binding phosphocholine conjugate is a direct 4-aminophenylphosphocholine covalently bound to human serum albumin. In a preferred embodiment, the present invention relates to a C-reactive protein-binding phosphocholine conjugate or a pharmaceutical composition thereof for use as a medicament for binding and/or neutralizing C-reactive protein in the blood, wherein the C-reactive protein-binding phosphocholine conjugate has the structure of the general formula (I):

where L represents a bond or linker; m comprises a number between 1 and 100; and HSA stands for human serum albumin. In the phosphocholine conjugates of formula (I) described here, –L– is defined as a linker or a single bond and is part of the phosphocholine fragment. Thus, the linker -L- is bound to the aromatic amine and to the carbonyl group of human serum albumin or forms a peptidic bond between the aromatic amine and the carbonyl group of human serum albumin. In a preferred embodiment, in which -L- is a linker, at least two carbon atoms of the linker are located between the aromatic amine and the carbonyl group of the HSA. The linker can be a PEN-P04423WO07 patent application (final).docx be an aliphatic chain, wherein the aliphatic chain optionally contains an inserted aromatic chain, or the aliphatic chain optionally contains 0 to 10 heteroatoms. The linker preferably contains 2 to 40 carbon atoms (including the carbon atoms of the optional side chains), more preferably 2 to 30, more preferably 2 to 20, more preferably 2 to 14, more preferably 2 to 12 and even more preferably 2 to 10 carbon atoms. The shortest atom chain between the aromatic amine and the HSA preferably consists of 2 to 14 atoms, more preferably 2 to 12 atoms, more preferably 2 to 10 atoms, and even more preferably 2 to 8 atoms. If the shortest chain (shortest possible connection between the aromatic amine and the HSA) consists of 2 to 6 atoms, these are preferably carbon atoms. If the shortest chain consists of 4 to 8 atoms, the chain may contain 1, 2, or 3 heteroatoms selected from O, N, and S. If the shortest chain consists of 9 to 14 atoms, the chain may contain 1, 2, Contain 3, 4, 5 or 6 heteroatoms selected from O, N and S. Also preferred is a linker -L- or a shortest atom chain that is completely or partially fluorinated. The linker -L- can have a 3-membered or a 4-membered or a 5-membered or a 6-membered saturated carbocycle or a 5-membered partially unsaturated (and non-aromatic) carbocycle or a 4-membered or a 5-membered or contain a 6-membered saturated oxygen heterocycle or a 4-membered or a 5-membered or a 6-membered saturated nitrogen heterocycle or a 6-membered aromatic carbocycle. The linker can also contain amide (-NH-CO-, -CO-NH-) and/or urea residues and preferably only one amide or only one urea residue. The linker can also contain substituents, preferably two substituents, such as R ¹⁰ and R ¹¹ , or four substituents, such as R ¹⁰ , R ¹¹ , R ¹⁵ and R ¹⁴ , which have the meaning described here and are preferably selected from: -F, –Cl, –CH3, –C2H5, –C3H7, –C5H9, –C6H13, –OCH3, –OC2H5, –CH2F, –CHF2, –CF3, –C(O)–NH2, –SCH3, –SC2H5, –NHC( O)CH3, –N(CH3)2, and –N(C2H5)2; If the linker -L- is fluorinated, then more than two F substituents are preferred. PEN-P04423WO07 Patent application (final).docx The linker is preferably selected from: -CH2-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2) 7–, –(CH2)8–, –(CH2)9–, –(CH2)10–, –CF2–, –(CF2)2–, –(CF2)3–, –(CF2)4–, – (CF2)5–, –(CF2)6–, –(CF2)7–, –(CF2)8–, –(CF2)9–, –(CF2)10–, –(CH2)2–O–( CH2)2–, –CH2–O–(CH2)3–, –(CH2)3–O–CH2–, –CH2–O–(CH2)2–, –(CH2)2–O–CH2–, – (CH2)3–O–(CH2)2–, –(CH2)2–O–(CH2)3–, –(CH2)4–O–CH2–, –CH2–O–(CH2)4–, – L ^a –, –L ^a –L ^e –, –L ^a –L ^b –L ^e –, –L ^a –L ^b –L ^d –L ^c –L ^e – and –L ^a –L ^d –L ^e – ; where –L ^a – is selected from: –(CH2)o–, –(CF2)o–, –(CH2–CH2–O)o–C2H4–,

^R10

; –L ^b – and –L ^c – are independently selected from: –O–,

PEN-P04423WO07 Patent application (final).docx , ; R ⁹ and R ¹⁸ are independently selected from: -CH3, -C2H5, -C3H7 and -C(O)CH3; PEN-P04423WO07 Patent application (final).docx R ¹⁰ , R ¹¹ , R ¹² , R ^{13 , R 14} ^, R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁹ , R ²⁰ , R ²¹ and R ²² are independently selected from: -H, -F, -Cl, –CH3, –C2H5, –C3H7, –C5H9, –OCH3, –OC2H5, –CH2F, –CHF2, –CF3, –C(O)–NH2, –SCH3,

–NHC(O)CH3, –N(CH3)2 and –N(C2H5)2; o, q, p1 and p2 are independently an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10. Likewise preferred is a linker -L- selected from:

, where a is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, b is an integer selected from 1, 2, 3 and 4. In a further preferred embodiment, the present invention relates to a C-reactive protein-binding phosphocholine conjugate or a pharmaceutical composition thereof for use as a medicament for binding and/or neutralizing C-reactive protein in the blood, wherein the C-reactive protein-binding phosphocholine conjugate Conjugate has the structure of the general formula (II):

where m comprises a number between 1 and 100; and HSA stands for human serum albumin. The inventor has surprisingly discovered that the molecular ratio m of 4-aminophenylphosphocholine to human serum albumin is crucial for the binding of the APPC-HSA conjugate to CRP and the inhibition and/or blocking of the APPC-HSA conjugate-CRP complex to the complement protein C1q. This suppresses complement activation, in PEN-P04423WO07 patent application (final).docx proteins can be formed that can locally destroy cells and tissue. In cooperation with immune cells, these proteins can increase their cytotoxicity, damage cell groups and kill cells (“membrane attack complex”), but also kill bacteria locally. In excess, activated complement proteins or peptides can also trigger systemic anaphylactic shock (C3a, C4a, C5a = anaphylatoxins). The APPC-HSA conjugates described herein are able to bind to the CRP in such a way that subsequent complexation with the complement protein C1q no longer occurs or only occurs to a lesser extent. This stops, reduces or even suspends the proedematous and pronecrotic effects of CRP in diseases such as heart attacks and strokes. Ultimately, this can stop the spread of damage and scars in the ischemic tissue and reduce or completely prevent an infarction scar after a heart attack. The molecular ratio m of 4-aminophenylphosphocholine to human serum albumin in the conjugates of the general formula (I) and (II) is preferably between 1 and 100, more preferably between 1 and 50, more preferably between 1 and 30, even more preferably between 1 and 20, more preferably between 2 and 15 and most preferably between 5 and 10. Preferably the molecular ratio m of 4-aminophenylphosphocholine to human serum albumin in the conjugates of the general formula (I) and (II) is between 35 and 40 more preferably between 30 and 35, even more preferably between 25 and 30, even more preferably between 20 and 25, even more preferably between 15 and 20, even more preferably between 10 and 15, even more preferably between 5 and 10 and most preferably between 1 and 5. Preferably the molecular ratio m of 4-aminophenylphosphocholine to human serum albumin in the conjugates of the general formula (I) and (II) is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. In order to prevent the aggregation of CRP-bound phosphocholine conjugates and thus minimize the risk of glomerulonephritis, the molecular ratio m of 4-aminophenylphosphocholine to human serum albumin in the APPC -HSA conjugate in the conjugates of general formula (I) and (II) preferably not greater than 3, more preferably not greater than 4, nor PEN-P04423WO07 patent application (final).docx more preferably not greater than 5, more preferably not greater than 6, more preferably not greater than 7, even more preferably not greater than 8, even more preferably not greater than 9, even more preferably not greater than 10. The APPC-HSA conjugates described herein can from phosphocholine and human serum albumin using the methods known from the prior art for the synthesis of peptide conjugates. Human serum albumin has a large number of functional groups known to those skilled in the art, via which the phosphocholine can be covalently bound. This functional group can be, among other things, a primary amino group of a lysine residue that reacts with an active ester, a carboxyl group of a glutamate or aspartate residue or a thiol group of a cysteine residue. In particular, peptide coupling reagents such as carbodiimides (including dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)), phosphonium salts (including BOP reagent, PyBOP, PyBrOP and PyOxime), immonium salts (including BOMI and BDMP), Aminium salts (including HBTU, TBTU, HATU, HCTU and TATU), Uronium salts (including TNTU, TPTU, TOTU, TDBTU, COMU, COMBU, TOMBU and TSTU), Imidazolium salts (including CBMIT, BOI, CIP, CIB and CMBI) or carbonyldiimidazole are suitable for the covalent binding of the APPC to a functional group of the amino acid side chain of the HSA. Active esters are also suitable for coupling APPC to HSA. Preferred active esters are N-(γ-maleimidobutyryloxy) sulfosuccinimide ester (sulfo-GMBS), succinimidyl (4-iodoacetyl) aminobenzoate (sulfo-SIAB), succinimidyl 3-(bromocetamido) propionate (SBAP), disuccinimidyl glutarate (DSG), disuccinimidyl adipate (DSA), 2-pyridyldithiol-tetraoxatetradecane-N-hydroxysuccinimide (PEG-4-SPDP), bis-(4-nitrophenyl) adipate and bis-(4-nitrophenyl) succinate. In the absence of a linker, the 4-aminophenylphosphocholine can be covalently linked directly to a carboxyl group of a glutamate or aspartate residue using a peptide coupling reagent. To introduce a linker, a functional group of the HSA (carboxylate) or the aromatic amine of the APPC can first be activated with a peptide coupling reagent or active ester and then reacted with the linker. The inventor has discovered that the APPC-HSA conjugates described herein efficiently bind CRP in the bloodstream and are therefore particularly relevant to PEN-P04423WO07 patent application (final).docx Suitable for the treatment of diseases associated and/or caused by elevated CRP levels. An elevated CRP level herein means a C-reactive protein blood level of preferably >5 mg/L, more preferably >10 mg/L, even more preferably >15 mg/L, even more preferably >20 mg/L, still more preferably from >25 mg/L, even more preferably from >30 mg/L, even more preferably from >50 mg/L, even more preferably from >75 mg/L, even more preferably from >100 mg/L, even more preferably from >150 mg /L and most preferably >200 mg/L at any time during the disease. Thus, the present invention relates to a C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof for use in the treatment and/or prevention of diseases caused and/or by a C-reactive protein blood level of >5 mg/L are associated, the C-reactive protein binding phosphocholine conjugate comprising a 4-aminophenylphosphocholine covalently bound to human serum albumin (HSA). In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or the pharmaceutical composition thereof for use in the treatment and/or prevention of diseases caused by a C-reactive protein blood level of >5 mg/L and/or are associated, the structure of the general formula (I), where L and m have the meanings described herein. Preferably L is a linker selected from:

, where a is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, b is an integer selected from 1, 2, 3 and 4. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and PEN-P04423WO07 patent application (final).docx 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or the pharmaceutical composition thereof for use in the treatment and/or prevention of diseases caused by a C-reactive protein blood level of >5 mg/L and/or are associated, the structure of the general formula (II), where m has the meaning described herein. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. However, the diseases associated and/or caused by elevated CRP levels do not include atherosclerosis. In atherosclerosis, an elevated CRP level of >20 mg/L in the blood is not regularly observed. Thus, the present invention relates to a C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof for use in the treatment and/or prevention of diseases caused by a C-reactive protein blood level of >20 mg/L and/or are associated, the C-reactive protein binding phosphocholine conjugate being a PEN-P04423WO07 patent application (final).docx Human serum albumin (HSA) comprises covalently bound 4-aminophenylphosphocholine, the disease not being atherosclerosis. In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or the pharmaceutical composition thereof for use in the treatment and/or prevention of diseases caused by a C-reactive protein blood level of >20 mg/L and/or are associated, the structure of the general formula (I), where L and m have the meanings described herein. Preferably L is a linker selected from:

, where a is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, b is an integer selected from 1, 2, 3 and 4. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or the pharmaceutical composition thereof for use in the treatment and/or prevention of diseases caused by a C-reactive protein blood level of >20 mg/L and/or associated PEN-P04423WO07 patent application (final).docx are, the structure of the general formula (II), where m has the meaning described herein. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. The diseases that are associated and/or caused by an increased CRP level are preferably acute diseases in which an increased CRP level (as described here) is observable in the patient within 1 to 5 days . Preferably, these diseases are associated and/or caused by an increase in CRP levels of >20 mg/L within 1 to 5 days. Preferably, these diseases are associated and/or caused by an increase in CRP levels of >20 mg/L within 1 to 4 days. Preferably, these diseases are associated and/or caused by an increase in CRP levels of >20 mg/L within 1 to 3 days. Preferably, these diseases are associated and/or caused by an increase in CRP levels of >20 mg/L within 1 to 2 days. Thus, the present invention relates to a C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof for use in the treatment and/or prevention of diseases caused by an acute increase in C-reactive protein blood levels of >20 mg/L and/or associated, wherein the C-reactive protein-binding phosphocholine conjugate comprises a 4-aminophenylphosphocholine covalently bound to human serum albumin (HSA). PEN-P04423WO07 Patent application (final).docx In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or pharmaceutical composition thereof is for use in the treatment and/or prevention of diseases caused by an acute increase in C-reactive protein blood levels of >20 mg/L and/or associated, the structure of the general formula (I), where L and m have the meanings described herein. Preferably L is a linker selected from:

, where a is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, b is an integer selected from 1, 2, 3 and 4. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or pharmaceutical composition thereof is for use in the treatment and/or prevention of diseases caused by an acute increase in C-reactive protein blood levels of >20 mg/L and/or associated, the structure of the general formula (II), where m has the meaning described herein. PEN-P04423WO07 Patent application (final).docx Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. The diseases that are associated with and/or caused by an increased CRP level include, among others, tumor diseases, inflammatory diseases, metabolic diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, postoperative conditions and infectious diseases. The present invention therefore relates to a C-reactive protein-binding phosphocholine conjugate or a pharmaceutical composition thereof for use in the treatment and/or prevention of diseases selected from tumor diseases, inflammatory diseases, metabolic diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, and postoperative conditions and infectious diseases, wherein the C-reactive protein binding phosphocholine conjugate comprises a 4-aminophenylphosphocholine covalently bound to human serum albumin (HSA). The present invention also relates to a method for the treatment and/or prevention of diseases selected from tumor diseases, inflammatory diseases, metabolic diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, postoperative conditions and infectious diseases in a patient, wherein the patient is provided with a C-reactive protein binding Phosphocholine conjugate or a pharmaceutical composition thereof is administered to lower the CRP level in the patient's blood. PEN-P04423WO07 Patent application (final).docx The treatment and prevention of cardiovascular diseases such as heart attack, cardiac arrest and stroke are preferred. In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or the pharmaceutical composition thereof for use in the treatment and/or prevention of diseases selected from tumor diseases, inflammatory diseases, metabolic diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, postoperative conditions and infectious diseases, the structure of general formula (I), where L and m have the meanings described herein. Preferably L is a linker selected from:

, where a is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, b is an integer selected from 1, 2, 3 and 4. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or the pharmaceutical composition thereof has the PEN-P04423WO07 patent application (final).docx Use in the treatment and/or prevention of diseases selected from tumor diseases, inflammatory diseases, metabolic diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, postoperative conditions and infectious diseases, the structure of the general formula (II), where m has the meaning described herein. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. Preferably, the C-reactive protein binding phosphocholine conjugate described herein or the pharmaceutical composition thereof relates to the treatment and/or prevention of tumor diseases selected from adenocarcinoma, choroidal melanoma, acute leukemia, acoustic neuroma, ampullary carcinoma, anal carcinoma, astrocytoma, basal cell carcinoma, pancreatic cancer, Desmoid tumor, bladder cancer, bronchial carcinoma, breast cancer, Burkitt lymphoma, corpus cancer, CUP syndrome (carcinoma of unknown origin), colon cancer, small intestinal cancer, small intestinal tumors, ovarian cancer, endometrial carcinoma, ependymoma, epithelial cancers, Ewing tumors, gastrointestinal tumors, stomach cancer, Gallbladder cancer, gallbladder carcinomas, uterine cancer, cervical cancer, cervix, glioblastomas, gynecological tumors, ear, nose and throat tumors, hematological neoplasms, hairy cell leukemia, urethral cancer, skin cancer, skin-testicular cancer, brain tumors (gliomas), brain metastases, testicular cancer, pituitary tumor, carcinoids, Kaposi -Sarcoma, larynx cancer, germ cell tumor, bone cancer, colon cancer, head and neck tumors (tumors of the ear, nose and throat area), colon cancer, craniopharyngiomas, oral cancer (cancer of the mouth and lips), cancer of the central nervous system, liver cancer, liver metastases , leukemia, eyelid tumor, lung cancer, lymph node cancer (Hodgkin/Non-Hodgkin), PEN-P04423WO07 patent application (final).docx Lymphoma, gastric cancer, malignant melanoma, malignant neoplasm, malignant tumors of the gastrointestinal tract, breast carcinoma, rectal cancer, medulloblastoma, melanoma, meningiomas, Hodgkin's disease, mycosis fungoides, nasal cancer, neuroma, neuroblastoma, kidney cancer, renal cell carcinoma, non-Hodgkin's lymphoma, oligodendroglioma, Esophageal carcinoma, osteolytic carcinoma and osteoplastic carcinoma, osteosarcoma, ovarian carcinoma, pancreatic carcinoma, penile cancer, plasmocytoma, prostate cancer, pharyngeal cancer, rectal carcinoma, retinoblastoma, vaginal cancer, thyroid carcinoma, Schneeberger disease, esophageal cancer, spinal cell carcinoma, T-cell lymphoma (mycosis fungoides), thymoma, Tubal carcinoma, eye tumors, urethral cancer, urological tumor, urothelial carcinoma, vulvar cancer, appearance of warts, soft tissue tumors, soft tissue sarcoma, Wilms tumor, cervical carcinoma and tongue cancer. Preferably, the C-reactive protein binding phosphocholine conjugate described herein or the pharmaceutical composition thereof relates to the treatment and/or prevention of autoimmune diseases selected from asthma, diabetes, rheumatic diseases, AIDS, rejection of transplanted organs and tissues, rhinitis, chronic obstructive pulmonary diseases, Osteoporosis, ulcerative colitis, sinusitis, lupus erythematosus, recurrent infections, atopic dermatitis/eczema and occupational allergies, food allergies, drug allergies, severe anaphylactic reactions, anaphylaxis, manifestations of allergic diseases, primary immunodeficiency, antibody deficiency states, cell-mediated immunodeficiency, severe combined immunodeficiency, DiGeorge syndrome, hyper-IgE syndrome, Wiskott-Aldrich syndrome, ataxia telangiectasia, immune-mediated cancers, leukocyte defects, autoimmune diseases, systemic lupus erythematosus, rheumatoid arthritis (RA), multiple sclerosis (MS), immune-mediated or type 1-Diabetes mellitus, immune-mediated glomerulonephritis, scleroderma, pernicious anemia, alopecia, pemphigus, pemphigus vulgaris, myasthenia gravis, inflammatory bowel disease, Crohn's disease, psoriasis, autoimmune thyroid disease, Hashimoto's thyroiditis, dermatomyositis, Goodpasture syndrome, myasthenia gravis pseudoparalytica, ophthalmia sympathetica, phacogenic uveitis, chronic aggressive hepatitis, primary biliary cirrhosis, autoimmune hemolytic anemia and Werlhof disease. Preferably, the C-reactive protein binding phosphocholine conjugate described herein or the pharmaceutical composition thereof relates to the treatment and/or prevention of infectious diseases selected from AIDS, PEN-P04423WO07 patent application (final).docx alveolar echinococcosis (AHD, echinococcosis), amebiasis (Entamoeba histolytica infection), angiostrongylus infection, anisakiasis, anthrax, babesiosis (Babesia infection), Balantidium infection (balantidiosis), Baylisascaris infection (raccoon roundworm), schistosomiasis, schistosomiasis, Blastocystis hominis infection (blastomycosis), Lyme disease, botulism, Brainerd's diarrhea, brucellosis, BSE (Bovine Spongiform Encephalopathy), candidiasis, capillariasis (Capillaria infection), CFS (chronic fatigue syndrome), Chagas disease (American trypanosomiasis), chickenpox ( Varicella zoster virus), Chlamydia pneumoniae infection, cholera, chronic fatigue syndrome, CJD (Creutzfeldt-Jakob disease), clonorchiasis (Clonorchis infection), LMC (larva migrans cutanea, hookworm infection), coccidioidomycosis, conjunctivitis, coxsackievirus A16 ( hand, foot and mouth disease), cryptococcosis, Cryptosporidium infection (cryptosporidiosis), Culex mosquito (vector of West Nile virus), larva migrans cutanea (LMC), cyclosporosis (cyclospora infection), cysticercosis (neurocysticercosis), Cytomegalovirus infection, dengue/dengue fever, Dipylidium infection (dog and cat flea tapeworm), Ebola virus hemorrhagic fever, echinococcosis (alveolar echinococcosis), encephalitis, Entamoeba coli infection, Entamoeba dispar infection, Entamoeba hartmanni infection, Entamoeba histolytica infection (amoebiasis), Entamoeba polecki infection, enterobiasis (pinworm infection), enterovirus infection (non-polio), Epstein-Barr virus infection, Escherichia coli infection, foodborne infection, foot and mouth disease, fungal Dermatitis, gastroenteritis, group A streptococcal disease, group B streptococcal disease, Hansen's disease (leprosy), Hantaviral pulmonary syndrome, head lice infestation (pediculosis), Helicobacter pylori infection, hematological disease, Hendra virus infection, hepatitis (HCV, HBV), herpes zoster (shingles), HIV infection, human Ehrlichiosis, human parainfluenza virus infection, influenza, isosporiosis (isospora infection), Lassa fever, leishmaniasis, Kala-azar (Kala-azar-, Leishmania infection), leprosy, lice (body lice, head lice, pubic lice), Lyme disease, malaria, Marburg virus hemorrhagic fever, measles, meningitis, mosquito-borne diseases, Mycobacterium avium complex (MAC) infection, Naegleria -Infection, nosocomial infections, non-pathogenic intestinal amoeba infection, onchocerciasis (river blindness), opistorchosis (Opisthorchis infection), parvovirus infection, plague, PCP (Pneumocystis carinii pneumonia), polio, Q fever, rabies, respiratory syncytial -Virus (RSV) infection, rheumatic fever, Rift Valley fever, river blindness (onchocerciasis), rotavirus infection, roundworm infection, salmonellosis, Salmonella enteritidis, scabies, shigellosis, shingles, sleeping sickness, smallpox, PEN-P04423WO07 patent application (final) .docx Streptococcal infection, tapeworm infection (Taenia infection), tetanus, toxic shock syndrome, tuberculosis, ulcers (stomach ulcer), Valley fever, Vibrio parahaemolyticus infection, Vibrio vulnificus infection, viral hemorrhagic fever, warts, water-borne infectious diseases , West Nile virus infection (West Nile encephalitis), whooping cough, yellow fever, tuberculosis, leprosy and meningitis caused by mycobacteria. Preferably, the C-reactive protein binding phosphocholine conjugate described herein or the pharmaceutical composition thereof relates to the treatment and/or prevention of inflammatory diseases selected from inflammatory diseases of the central nervous system (CNS), inflammatory rheumatic diseases, inflammatory diseases of the blood vessels, inflammatory diseases of the middle ear , inflammatory bowel disease, inflammatory skin disease, inflammatory disease uveitis and inflammatory disease of the larynx. Preferably, the C-reactive protein binding phosphocholine conjugate described herein or the pharmaceutical composition thereof relates to the treatment and/or prevention of respiratory diseases selected from bronchial asthma, pediatric asthma, severe asthma, acute asthma attack, chronic bronchitis, COPD (chronic obstructive pulmonary disease) and interstitial lung diseases such as pneumonia, radiation-induced pneumonitis or fibrosis, collagen diseases such as lupus erythematosus, systemic scleroderma or sarcoidosis, granulomatosis such as Boeck's disease, idiopathic interstitial pneumonia or idiopathic pulmonary fibrosis (IPF). Preferably, the C-reactive protein binding phosphocholine conjugate described herein or the pharmaceutical composition thereof relates to the treatment and/or prevention of metabolic diseases selected from adrenogenital syndrome, alkaptonuria, alpha-1-antitrypsin deficiency, diabetes mellitus (diabetes), erythropoietic protoporphyria (disease from the group of porphyrias), galactosemia, hypophosphatasia (Rathbuin syndrome), hypothyroidism (underactive thyroid), ketoacidosis, ketosis (acetonemia, acetonuria), Lesch-Nyhan syndrome (hyperuricemia syndrome or hyperuricosis), methylmalonic aciduria (MMA), myoadenylate deaminase deficiency (MADD), Addison's disease (hypadrenocorticism), Conn's disease (hyperaldosteronism), Cushing's disease, Fabry's disease, Gaucher's disease, Hunter's disease (mucopolysaccharidosis PEN-P04423WO07 patent application (final).docx Type II), cystic fibrosis (cystic fibrosis), phenylketonuria, porphyrias, thesaurismosis (storage disease) and uricopathy (gout). Preferably, the C-reactive protein binding phosphocholine conjugate described herein or the pharmaceutical composition thereof relates to the treatment and/or prevention of the condition after operations, after organ and tissue and bone marrow transplants, after plastic surgical operations, in particular those with systemic anesthesia, after therapeutic irradiation with different external physical sources (such as α-, ß-, γ-, positrons) as well as diagnostics and therapy with radionuclide drugs administered in vivo. In a preferred embodiment, the present invention relates to a C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof for use in the treatment of ischemia. Ischemia hinders or stops cellular metabolism. Ischemia caused by throttling or interruption of blood flow is accompanied by a lack of oxygen in the affected area. This can lead to necrosis and a heart attack. In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or pharmaceutical composition thereof for use in the treatment and/or prevention of ischemia has the structure of the general formula (I), where L and m have the meanings described herein. Preferably L is a linker selected from:

, where a is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, b is an integer selected from 1, 2, 3 and 4. Preferably m is between 1 and 100, more preferably between 1 and 50, more preferably between 1 and 30, more preferably between 1 and 20, more preferably between 2 and 15 and most preferably between 5 and 10. PEN-P04423WO07 Patent application (final) .docx It is also preferred if m is between 35 and 40, even more preferably between 30 and 35, even more preferably between 25 and 30, even more preferably between 20 and 25, even more preferably between 15 and 20, even more preferably between 10 and 15, even more preferably between 5 and 10 and most preferably between 1 and 5. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or the pharmaceutical composition thereof for use in the treatment and/or prevention of ischemia has the structure of the general formula (II), where m has the meaning described herein. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or the pharmaceutical composition thereof for use in the treatment and/or prevention of diseases selected from cardiovascular arrest, stroke and pancreatitis has the structure of the general formula (I) , where L and m have the meanings described herein. Preferably L is a linker selected from:

PEN-P04423WO07 Patent application (final).docx

, where a is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, b is an integer selected from 1, 2, 3 and 4. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or the pharmaceutical composition thereof for use in the treatment and/or prevention of diseases selected from cardiovascular arrest, stroke and pancreatitis has the structure of the general formula (II) , where m has the meaning described herein. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not greater than 3, more preferably not greater than 4, more preferably not greater than 5, more preferably not greater than 6, even more preferably not greater than 7, nor PEN-P04423WO07 patent application (final).docx more preferably not greater than 8, more preferably not greater than 9, even more preferably not greater than 10. In a further preferred embodiment, the present invention relates to a C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof for use in the treatment and/or prevention of autoimmune diseases, the autoimmune disease being selected from rheumatoid arthritis, inflammatory bowel disease, lupus, asthma , diabetes, rheumatic diseases, AIDS, rejection of transplanted organs and tissues, rhinitis, chronic obstructive pulmonary diseases, osteoporosis, ulcerative colitis, sinusitis, lupus erythematosus, recurrent infections, atopic dermatitis / eczema and occupational allergies, food allergies, drug allergies, severe anaphylactic reactions, Anaphylaxis, manifestations of allergic diseases, primary immune deficiency, antibody deficiency states, cell-mediated immune deficiency, severe combined immune deficiency, DiGeorge syndrome, hyper-IgE syndrome, Wiskott-Aldrich syndrome, ataxia telangiectasia, immune-mediated cancers, leukocyte defects, multiple sclerosis (MS), immune-mediated or type 1 diabetes mellitus, immune-mediated glomerulonephritis, scleroderma, pernicious anemia, alopecia, pemphigus, pemphigus vulgaris, myasthenia gravis, inflammatory bowel disease, Crohn's disease, psoriasis, autoimmune thyroid disease, Hashimoto's thyroiditis, Dermatomyositis, Goodpasture syndrome, myasthenia gravis pseudoparalytica, sympathetic ophthalmia, phacogenic uveitis, chronic aggressive hepatitis, primary biliary cirrhosis, autoimmune hemolytic anemia and Werlhof disease; and wherein the C-reactive protein binding phosphocholine conjugate comprises a 4-aminophenylphosphocholine covalently bound to human serum albumin (HSA). In a preferred embodiment, the C-reactive protein-binding phosphocholine conjugate or the pharmaceutical composition thereof for use in the treatment and/or prevention of diseases of infectious diseases, the infectious diseases caused by bacteria, viruses, prions, parasites, fungi, induced, initiated and/or amplified and/or triggered by irritant, traumatic, metabolic, allergic, autoimmunological or idiopathic causes, the structure of the general formula (I), where L and m have the meanings described herein. Preferably, L is a linker selected from: PEN-P04423WO07 patent application (final).docx , where a is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, b is an integer selected from 1, 2, 3 and 4. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or the pharmaceutical composition thereof for use in the treatment and/or prevention of infectious diseases, wherein the infectious diseases are caused, induced, initiated and caused by bacteria, viruses, prions, parasites, fungi /or aggravated and/or triggered by irritant, traumatic, metabolic, allergic, autoimmunological or idiopathic causes, the structure of the general formula (II), where m has the meaning described herein. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, PEN-P04423WO07 patent application (final).docx more preferably between 5 and 10 and most preferably between 1 and 5. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. In a preferred embodiment, the C-reactive protein-binding phosphocholine conjugate or the pharmaceutical composition thereof for use in the treatment and/or prevention of infectious diseases, the infectious disease being a disease triggered by coronaviruses, in particular SARS-CoV-2, the structure of the general formula (I), where L and m have the meanings described herein. Preferably L is a linker selected from:

, where a is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, b is an integer selected from 1, 2, 3 and 4. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. PEN-P04423WO07 Patent application (final).docx In a preferred embodiment, the C-reactive protein-binding phosphocholine conjugate or the pharmaceutical composition thereof for use in the treatment and/or prevention of infectious diseases, the infectious disease being a disease triggered by coronaviruses, in particular SARS-CoV-2, has the structure the general formula (II), where m has the meaning described herein. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. The connection between the indications to be treated according to the invention and the increased CRP levels in the blood, ie CRP levels of 20 mg/L and more (eg 20 mg/L to 100 mg/L), is known to those skilled in the art. The inventors have already scientifically proven in previous publications that lowering the CRP level in the blood through apheresis treatment can be used for the prophylaxis and treatment of the indications described herein. The present patent application now scientifically proves that the disclosed 4-aminophenylphosphocholine-human serum albumin conjugates (APPC-HSA conjugates) reduce CRP levels and can therefore be used for the prophylaxis and/or treatment of the diseases described herein. Since animal experiments should be avoided if possible due to the FDA's new premise, since it has been shown that the data obtained with animals are often not transferable to humans, it has now become almost impossible to get an animal experiment approved by an ethics committee is intended to provide in-vivo evidence of binding of an active ingredient to CRP. This applies to all animal species, including rodents such as mice and rats. PEN-P04423WO07 Patent application (final).docx In order to meet the patent offices' requirements regarding sufficient disclosure and sufficient proof of inventive step, the in vivo situation was simulated as best as possible. In addition, the use of human serum albumin already restricts the conduct of animal experiments and in a mouse experiment a mouse serum albumin conjugate would have had to be produced and tested with the questionable result as to whether these data could have been transferred to the human serum albumin conjugates and humans. Thus, in Example 6, the human system was recreated using human blood plasma and binding of the APPC-HSA conjugates disclosed herein was demonstrated. Figure 5 clearly shows the CRP binding to the APPC-HSA conjugates according to the invention in a concentration-dependent manner. The binding of CRP in the blood plasma and thus the blockade of CPR in the blood increases reproducibly with the concentration of APPC-HSA conjugate as well as with the number of APPC molecules in an APPC-HSA conjugate. This experiment is therefore more meaningful than an animal experiment with, for example, mice using an APPC-mouse serum albumin conjugate. In another embodiment, the APPC-HSA conjugate described herein or the pharmaceutical composition thereof may be used in combination with extracorporeal procedures to lower CRP levels, such as dialysis or apheresis. In these procedures, the CRP is removed from blood plasma using affinity chromatographic columns loaded with CRP-binding material. The combination is useful for treating particularly high CRP levels of over 550 mg/L. Thus, the present invention relates to a C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof for use as a medicament for binding and/or neutralizing C-reactive protein in the blood in combination with an apheresis or dialysis procedure to lower C-reactive Protein level, wherein the C-reactive protein binding phosphocholine conjugate comprises a 4-aminophenylphosphocholine covalently bound to human serum albumin (HSA). In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or the pharmaceutical composition thereof has for use as a medicament for binding and/or neutralizing C-reactive PEN-P04423WO07 patent application (final).docx Protein in the blood in combination with an apheresis or dialysis procedure to reduce the C-reactive protein level has the structure of the general formula (I), where L and m have the meanings described herein. Preferably L is a linker selected from:

, where a is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, b is an integer selected from 1, 2, 3 and 4. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. In a preferred embodiment, the C-reactive protein binding phosphocholine conjugate or pharmaceutical composition thereof is for use as a medicament for binding and/or neutralizing C-reactive protein in the blood in combination with an apheresis or dialysis procedure to lower C-reactive Protein mirror has the structure of the general formula (II), where m has the meaning described herein. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 PEN-P04423WO07 patent application (final).docx and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. A further aspect of the present invention relates to pharmaceutical compositions for use as a medicament for binding and/or neutralizing C-reactive protein in the blood comprising a C-reactive protein binding phosphocholine-HSA conjugate, wherein the C-reactive protein binding phosphocholine conjugate 4-aminophenylphosphocholine covalently bound to human serum albumin (HSA). For use as a medicament for binding and/or neutralizing C-reactive protein in the blood, the pharmaceutical formulation may further comprise pharmaceutically acceptable carriers, excipients and/or diluents. The pharmaceutical compositions described herein may be prepared in a conventional solid or liquid carrier or diluent and a conventional pharmaceutically prepared excipient in appropriate dosage in a known manner. The pharmaceutical compositions described herein are typically administered in conjunction with suitable acceptable carriers selected with respect to the intended form of administration, for example, as powders for constitution, gels, elixirs, dispersible granules, syrups, suspensions and the like, and in accordance with conventional pharmaceutical practices . Also included are preparations in solid form intended to be converted into a liquid form shortly before use. These liquid forms include solutions, suspensions and emulsions. The pharmaceutical compositions described herein may be administered subcutaneously, by spray, by injection, intramuscularly, as a suppository or trans(epi)dermally. PEN-P04423WO07 Patent application (final).docx The C-reactive protein-binding phosphocholine conjugates described herein and the pharmaceutical compositions thereof described herein are preferably intended for the treatment of humans but can also be used in animals and in particular in horses and preferably riding and dressage horses. In a preferred embodiment, the C-reactive protein binding APPC-HSA conjugate contained in the pharmaceutical composition described herein is in a range of 1 mg/kg to 100 mg/kg, preferably 2 mg/kg to 100 mg/kg, preferably 5 mg/kg to 100 mg/kg, preferably 10 mg/kg to 100 mg/kg per body weight per day. In a preferred embodiment, the pharmaceutical composition for the treatment and/or prevention of diseases associated and/or caused by an elevated CRP level comprises the C-reactive protein binding phosphocholine conjugate having the structure of the general formula (I), wherein L and m have the meanings described herein and the C-reactive protein binding APPC-HSA conjugate in a range of 1 mg/kg to 100 mg/kg, preferably 2 mg/kg to 100 mg/kg, preferably 5 mg/kg up to 100 mg/kg, preferably 10 mg/kg to 100 mg/kg per body weight per day. Preferably L is a linker selected from:

, where a is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, b is an integer selected from 1, 2, 3 and 4. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 PEN-P04423WO07 patent application (final).docx and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. In a preferred embodiment, the pharmaceutical composition for the treatment and/or prevention of diseases associated and/or caused by an elevated CRP level comprises the C-reactive protein binding phosphocholine conjugate having the structure of the general formula (II), wherein m has the meaning described herein and the C-reactive protein-binding APPC-HSA conjugate in a range from 1 mg/kg to 100 mg/kg, preferably 2 mg/kg to 100 mg/kg, preferably 5 mg/kg to 100 mg/kg, preferably 10 mg/kg to 100 mg/kg per body weight per day. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. In a further preferred embodiment, the APPC-HSA conjugate described herein or the pharmaceutical composition thereof can be used in combination with at least one complement blocker to bind and/or neutralize C-reactive protein in the blood. Preferably, the complement blocker inhibits the complement protein(s) C3 and/or C5 by acting on PEN-P04423WO07 patent application (final).docx binds an active site of the complement protein(s) C3 and/or C5. The complement blocker also prevents complement activation, which stops the spread of damage and scarring in the ischemic tissue and reduces or completely prevents an infarction scar after a heart attack. The present invention therefore also relates to a C-reactive protein-binding phosphocholine conjugate or a pharmaceutical formulation for use as a medicament for binding and/or neutralizing C-reactive protein in the blood, comprising a C-reactive protein-binding phosphocholine conjugate, wherein the C - Reactive protein-binding phosphocholine conjugate comprises a 4-aminophenylphosphocholine covalently bound to human serum albumin, in combination with at least one complement blocker. In a preferred embodiment, the C-reactive protein-binding phosphocholine conjugate or the pharmaceutical composition thereof for use as a medicament for binding and/or neutralizing C-reactive protein in the blood in combination with at least one complement blocker has the structure of the general formula (I) , where L and m have the meanings described herein. Preferably L is a linker selected from:

, where a is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, b is an integer selected from 1, 2, 3 and 4. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not greater than 3, PEN-P04423WO07 patent application (final).docx more preferably not greater than 4, more preferably not greater than 5, more preferably not greater than 6, more preferably not greater than 7, more preferably not greater than 8, more preferably not greater than 9, even more preferably not greater than 10. In a preferred embodiment, the C-reactive protein-binding phosphocholine conjugate or the pharmaceutical composition thereof for use as a medicament for binding and/or neutralizing C-reactive protein in the blood in combination with at least one complement blocker has the structure of the general formula (II) , where m has the meaning described herein. Preferably m is between 1 and 100, more preferably between 1 and 50, even more preferably between 1 and 30, even more preferably between 1 and 20, even more preferably between 2 and 15 and most preferably between 5 and 10. It is also preferred if m is between 35 and 40, more preferably between 30 and 35, more preferably between 25 and 30, more preferably between 20 and 25, more preferably between 15 and 20, more preferably between 10 and 15, more preferably between 5 and 10 and most preferably between 1 and 5 lies. It is also preferred if m is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. Furthermore, it is preferred if m is not larger than 3, more preferably not larger than 4, even more preferably not larger than 5, even more preferably not larger than 6, even more preferably not larger than 7, even more preferably not larger than 8, even more preferably not larger than 9, more preferably not greater than 10. PEN-P04423WO07 Patent application (final).docx Description of the figures Figure 1 ELISA for binding CRP to APPC-HSA with increasing CRP concentration. The amount of bound CRP was detected using a MAK against human CRP. Figures 2 and 3 Concentration-dependent blockade of the binding of huCRP to the fixed HSA-APPC matrix by the test substances. The values are mean values (Mw) from three independent experimental approaches (in two approaches only the results from duplicate determinations were available). The measurement signal, the optical density, was converted into CRP amounts (mg/ml) using a reference curve. Figure 4 SDS gel of the HSA-APPC constructs. M: size marker, H1 - H5: constructs, HM: HSA Figure 5 CRP blocking by HSA-APPC constructs Figure 5 shows that the blockade is concentration dependent, both in relation to the amount of HSA-APPC used and the amount of APPC molecules per HSA molecule. By imitating the human in vivo blood system as much as possible, the result clearly shows that a blockade of CRP binding can also be achieved in the in vivo situation in human blood plasma and that there are no relevant disruptive factors. PEN-P04423WO07 Patent application (final).docx Examples Abbreviations APPC: 4-aminophenylphosphocholine, ligand for CRP BSA: Bovine serum albumin CRP: C reactive protein ELISA: Enzyme-Linked Immuno Sorbent Assay APPC- HSA: human serum albumin, coupled with APPC IgG: immunoglobulin G Cav.: Cavity MAK. Monoclonal antibody against CRP MTP: microtiter plate PBS: phosphate buffered physiological saline POD-anti Mouse: peroxidase, coupled to a secondary antibody against murine IgG S: laboratory shaker for MTP TMB: 3,3',5,5' tetramethylbenzidine, substrate for the POD, Color reagent Tween20: detergent, trade name Example 1: Synthesis of an APPC-HSA conjugate from the prior art The APPC-HSA conjugate was prepared according to the instructions from Journal of Immunological Methods 293 (2004) 1-11. For this purpose, 4 mg of human serum albumin was coupled with 4 mg of 4-aminophenylphosphocholine (APPC) in 0.1 M MES buffer (pH 4.5) in the presence of 2 mg of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The reaction mixture was then incubated at room temperature for 2 hours. The HSA conjugate was then dialyzed against PBS buffer (pH 7.4) at 4 °C. Example 2: Synthesis of APPC-HSA conjugates with different APPC loading APPC-HSA conjugates with an APPC loading of 1:1 to 50:1 were synthesized as described in Example 1, with the initial concentration of APPC adjusted accordingly has been. The molecular ratio of 4-aminophenylphosphocholine to human serum albumin was determined using MALDI. PEN-P04423WO07 Patent application (final).docx Example 3: ELISA to determine the CRP binding of the APPC-HSA conjugates Polystyrene microtiter plates were coated overnight at 4 ° C to 8 ° C with APPC-HSA conjugates in 0.1 M carbonate / bicarbonate buffer at pH 9, 6 incubated. The final volume of all wells was 100 µL. The plates were washed twice with phosphate buffer (PBS) and free binding sites were then blocked with 2% HSA solution in PBS (200 µL per well). CRP-containing samples (plasma or sera) were diluted appropriately in assay buffer and incubated for 1 hour at room temperature. CRP standard solutions with a defined concentration were prepared and used to create the binding curve (see Table 1). The plates were then washed again with PBS and the bound CRP was detected by incubation with biotinylated monoclonal antibody 5G4 against human CRP (diluted in assay buffer for 60 min). The wells were subsequently incubated with polymerized peroxidase dissolved in veronal buffer and the peroxidase activity was visualized with 3,3',5,5'-tetramethylbenzidine. The reaction was stopped after 10 minutes by adding 2 molar sulfuric acid and the absorbance was measured at 450 nm with a plate reader. Tab.1: Protocol for HSA-APPC and binding of CRP

PEN-P04423WO07 Patent application (final).docx

Tab.2: Optical density (OD) of the CRP quantity. The OD was measured using a standard MTP reader (96 well) immediately after step 6. The MW from two individual measurements are shown.

Example 4: This example shows how the test substances (HSA-APPC constructs or acetylated HSA-APPC constructs with different amounts of APPC per HSA molecule) block the binding of huCRP to the fixed BSA-APPC matrix. In this form, the BSA-APPC matrix fixed to the wall of microtiter plates simulates the apoptotic-looking state of ischemic cells in which the natural phosphocholine molecules ready for CRP binding are accessible on the cell surface. Only in this state are the cells vulnerable to CRP. PEN-P04423WO07 Patent application (final).docx The coupling of APPC to HSA or acHSA was carried out according to Example 1 with different and increasing concentrations of APPC. The result of the synthesis was then test substances with ratios of HSA to APPC: 1:5, 1:20, 1:40 and 1:80 (the latter not shown). When binding huCRP in the reference system (see Fig. 1), the binding capacity of the BSA-APPC matrix is largely exhausted with 2,500 ng CRP/ml (the molar ratio of BSA:APPC was 1:3.6). If CRP binds to the matrix in the presence of the test substances, the binding of huCRP to the matrix is reduced depending on the concentration. 2 and 3 show the percentage reduction in CRP binding to the fixed matrix, based on the reference system (without test substances, 100%). The experiments were carried out in microtiter plates according to Example 3. The experiments were carried out with both HSA-APPC and with acetylated HSA-APPC, with similar results for the latter. Table 3A. Experiments with HSA-APPC matrix

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Table 3B. Experiments with HSA-APPC matrix (Figure 2)

Table 4A. Experiments with acetylated HSA-APPC matrix

Table 4B. Experiments with acetylated HSA-APPC matrix (Figure 3) PEN-P04423WO07 patent application (final).docx

Example 5 HSA was coupled with various amounts of APPC. The following table shows the average number of APPC molecules per HSA molecule.

The constructs were loaded onto an SDS gel. The increase in size caused by the APPC can be clearly seen (see Fig. 4). Example 6 In another approach, HSA was coupled with various amounts of APPC. The number of APPC molecules per HSA molecule was 5, 20, 40 and 80. In order to reproduce the human in vivo situation as accurately as possible, human blood plasma was used in the following experiment. All relevant blood factors are found in the human blood plasma, which closely replicates the human in vivo situation. The BSA-APPC fixed to the bottom of the microtiter plate simulates the cell surface of the damaged cell. The blockade of CRP binding by the constructs is measured. The experiment was carried out three times. Human blood plasma containing 100 ng/mL CRP was mixed with different amounts of these HSA-APPC constructs 1:1 (vol:vol) and used in a BSA-APPC ELISA. CRP without additive and CRP mixed with HSA was used as control PEN-P04423WO07 patent application (final).docx used. Blocking CRP binding without additive was used as a starting point to calculate the blocking effect of the constructs. As Figure 5 shows, the blockade is concentration dependent. Table 6

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Claims

Claims 1. A C-reactive protein-binding phosphocholine conjugate or a pharmaceutical composition thereof for use as a medicament for binding and / or neutralizing C-reactive protein in the blood, wherein the C-reactive protein-binding phosphocholine conjugate is a human serum albumin covalently bound 4-aminophenylphosphocholine. 2. The C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof according to claim 1, wherein the phosphocholine conjugate has the structure of the general formula (I):

where L represents a bond or linker; m comprises a number between 1 and 100; and HSA stands for human serum albumin. 3. The C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof according to claim 1 or 2, wherein the molecular ratio m of 4-aminophenylphosphocholine to human serum albumin is between 1 and 50. 4. The C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof according to claim 1 or 2, wherein the molecular ratio m of 4-aminophenylphosphocholine to human serum albumin comprises between 5 and 10. 5. The C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof according to any one of claims 1 to 4 for use in the treatment and/or prevention of diseases, PEN-P04423WO07 patent application (final).docx caused by and/or associated with a C-reactive protein blood level >20 mg/L. 6. The C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof for use according to any one of claims 1 to 5, wherein the disease is selected from tumor diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, metabolic diseases, cardiovascular diseases, postoperative conditions and infectious diseases. 7. The C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof for use according to any one of claims 1 to 5, wherein the disease is a heart attack, cardiovascular arrest, a stroke or pancreatitis. 8. The C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof for use according to claim 6, wherein the autoimmune disease is selected from rheumatoid arthritis, inflammatory bowel disease, lupus, asthma, diabetes, rheumatic diseases, AIDS, rejection of transplanted organs and tissues , rhinitis, chronic obstructive pulmonary diseases, osteoporosis, ulcerative colitis, sinusitis, lupus erythematosus, recurrent infections, atopic dermatitis / eczema and occupational allergies, food allergies, drug allergies, severe anaphylactic reactions, anaphylaxis, manifestations of allergic diseases, primary immunodeficiency, antibody deficiency states, Cell-mediated immunodeficiency, severe combined immunodeficiency, DiGeorge syndrome, hyper-IgE syndrome, Wiskott-Aldrich syndrome, ataxia telangiectasia, immune-mediated cancers, leukocyte defects, multiple sclerosis (MS), immune-mediated or type 1 Diabetes mellitus, immune-mediated glomerulonephritis, scleroderma, pernicious anemia, alopecia, pemphigus, pemphigus vulgaris, myasthenia gravis, inflammatory bowel disease, Crohn's disease, psoriasis, autoimmune thyroid disease, Hashimoto's thyroiditis, dermatomyositis, Goodpasture syndrome, myasthenia gravis pseudoparalytica, ophthalmia sympathetic, phacogenic uveitis, chronic aggressive hepatitis, primary biliary cirrhosis, autoimmune hemolytic anemia, and Werlhof disease. PEN-P04423WO07 Patent application (final).docx 9. The C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof for use according to claim 5 or 6, wherein the infectious disease is caused, induced, initiated and/or aggravated by bacteria, viruses, prions, parasites, fungi and/or caused by irritant, traumatic, metabolic, allergic, autoimmunological or idiopathic causes. 10. The C-reactive protein-binding phosphocholine conjugate or a pharmaceutical composition thereof for use according to claim 6 or 9, wherein the infectious disease is a disease triggered by coronaviruses, in particular SARS-CoV-2. 11. The C-reactive protein binding phosphocholine conjugate or a pharmaceutical composition thereof for use according to any one of claims 5 to 10 in combination with an apheresis or dialysis method for lowering the C-reactive protein level. 12. The pharmaceutical composition for use according to any one of claims 5 to 11, wherein the pharmaceutical composition is administered orally, intratecally, intravenously or by inhalation. 13. The pharmaceutical composition for use according to any one of claims 5 to 12, wherein the C-reactive protein binding phosphocholine conjugate is administered in a range of 1 to 100 mg/kg per body weight per day. 14. The pharmaceutical composition for use according to any one of claims 5 to 13, further comprising a pharmaceutically acceptable carrier, an excipient and/or a diluent. 15. The pharmaceutical composition for use according to any one of claims 5 to 14, in combination with at least one complement blocker. PEN-P04423WO07 Patent application (final).docx