Abstract: The present invention relates to bispecific anti-CCL2 antibodies binding to two different epitopes on human CCL2, pharmaceutical compositions thereof, their manufacture, and use as medicaments for the treatment of cancers, inflammatory, autoimmune and ophthalmologic diseases.

Abstract: Herein is reported a method for the determination of the binding affinity of a binder and its ligand comprising the step of determining based on the result of an immunoassay the fraction of free binder in a sample comprising binder, ligand and binder-ligand-complexes for at least two different binder:ligand ratios in the sample, and if the determined fraction of free binder is not comparable for all used binder:ligand ratios then the binder:ligand ratio in the sample is lowered and the sample is re-analyzed by the same immunoassay, and calculating based on the fraction of free binder in the previous step the binding affinity for the binder to its ligand.

Abstract: The present invention relates to bispecific anti-CCL2 antibodies binding to two different epitopes on human CCL2, pharmaceutical compositions thereof, their manufacture, and use as medicaments for the treatment of cancers, inflammatory, autoimmune and ophthalmologic diseases.

Abstract: Herein is reported a method for determining the concentration of a therapeutic antibody in a tissue of an experimental animal to whom the therapeutic antibody had been administered, wherein the interference from residual blood in a tissue sample of the experimental animal, which is used for determining the concentration of the therapeutic antibody in said tissue, is reduced by applying an inert reference antibody that does not penetrate into said tissue, whereby the inert reference antibody is administered 2 to 10 minutes prior to obtaining the tissue and blood sample.

Abstract: Herein is reported a method for the determination of the binding affinity of a binder and its ligand comprising the step of determining based on the result of an immunoassay the fraction of free binder in a sample comprising binder, ligand and binder-ligand-complexes for at least two different binder:ligand ratios in the sample, and if the determined fraction of free binder is not comparable for all used binder:ligand ratios then the binder:ligand ratio in the sample is lowered and the sample is re-analyzed by the same immunoassay, and calculating based on the fraction of free binder in the previous step the binding affinity for the binder to its ligand.

Abstract: Herein is reported a method for determining free antigen of an antibody in an undiluted serum sample comprising the steps of a) applying the undiluted sample to a solid phase on which a capture antibody has been immobilized to form a capture antibody-antigen complex, wherein the capture antibody competes with the antibody for binding to a first epitope on the antigen, b) applying to the solid phase a tracer antibody to form a capture antibody-antigen-tracer antibody complex, wherein the tracer antibody specifically binds to a second epitope on the antigen, wherein the epitope of the tracer antibody is not overlapping with the epitope of the capture antibody on the antigen, and c) determining the free antigen of the antibody by determining the tracer antibody in the capture antibody-antigen-tracer antibody complex.

Abstract: The present invention relates to bispecific anti-CCL2 antibodies binding to two different epitopes on human CCL2, pharmaceutical compositions thereof, their manufacture, and use as medicaments for the treatment of cancers, inflammatory, autoimmune and ophthalmologic diseases.

Abstract: Herein is reported a method for the determination of the presence of anti-drug antibodies in a sample comprising the steps of incubating the sample with MgCl2 at a final concentration in the range of 1 N to 12 N; adding a tracer antibody and incubating the sample thereafter; incubating the isolated tracer antibody-anti-drug antibody-complexes with a detection antibody conjugated to a detectable label and determining the presence of anti-drug antibodies if a signal above a threshold level is obtained.

Abstract: Herein is reported a method for determining the concentration of a therapeutic antibody in a tissue of an experimental animal to whom the therapeutic antibody had been administered, wherein the interference from residual blood in a tissue sample of the experimental animal, which is used for determining the concentration of the therapeutic antibody in said tissue, is reduced, wherein the concentration of the therapeutic antibody in the tissue of the experimental animal is calculated with the following formula: C tmAb , tissue = C t ? m ? A ? b , tissue , det . C t ? i ? s ? sue , sample - C r ? e ? f ? m ? A ? b , tissue , det . C t ? i ? s ? sue , sample C r ? e ? f ? m ? A ? b , plasma . det . * C t ? m ? A ? b , plasma , det . wherein CtmAb,tissue,det.=obtained by determining the concentration of the therapeutic antibody in the tissue sample of the experimental animal, CtmAb,plasma,det.

Abstract: The present invention relates to a dosage and administration regimen of anti-C5 antibodies, particularly of the anti-C5 antibody Crovalimab, for use in a method of treating or preventing C5-related disease in a subject, including paroxysmal nocturnal hemoglobinuria (PNH). The dosage and treatment regimen of the present invention include the administration of an anti-C5 antibody, preferably of the anti-C5 antibody Crovalimab, with loading doses followed by the administration of (a) maintenance dose(s) of the anti-C5 antibody to the subject, wherein the initial administered loading dose is intravenously given to the subject and the remaining loading and maintenance doses are subcutaneously administered in a lower dosage as the intravenously administered loading dose.

Abstract: The present invention relates to a dosage and administration regimen of anti-C5 antibodies, particularly of the anti-C5 antibody Crovalimab, for use in a method of treating or preventing C5-related disease in a subject, including paroxysmal nocturnal hemoglobinuria (PNH). The dosage and treatment regimen of the present invention include the administration of an anti-C5 antibody, preferably of the anti-C5 antibody Crovalimab, with loading doses followed by the administration of (a) maintenance dose(s) of the anti-C5 antibody to the subject, wherein the initial administered loading dose is intravenously given to the subject and the remaining loading and maintenance doses are subcutaneously administered in a lower dosage as the intravenously administered loading dose.

Abstract: Herein is reported a method for the determination of a bispecific antibody in a serum-containing sample comprising the steps of first incubating a solid phase to which a capture antibody specifically binding to the bispecific antibody has been immobilized with the sample to form an immobilized capture antibody-bispecific antibody-complex, thereafter incubating the solid phase with a replacement antibody that competes with the capture antibody for binding to the bispecific antibody and thereby forming a solution comprising a replacement antibody-bispecific antibody-complex, and determining in the solution the replacement antibody-bispecific antibody-complex.

Abstract: Herein is reported a method for determining the concentration of a therapeutic antibody in a tissue of an experimental animal to whom the therapeutic antibody had been administered, wherein the interference from residual blood in a tissue sample of the experimental animal, which is used for determining the concentration of the therapeutic antibody in said tissue, is reduced, wherein the concentration of the therapeutic antibody in the tissue of the experimental animal is calculated with the following formula: C tmAb , tissue = C tmAb , tissue , det . C tissue , sample - C refmAb , tissue , det . C tissue , sample C refmAb , plasma . det . * C tmAb , plasma , det . wherein CtmAb,tissue,det.=obtained by determining the concentration of the therapeutic antibody in the tissue sample of the experimental animal, CtmAb,plasma,det.

Abstract: The present invention relates to bispecific anti-CCL2 antibodies binding to two different epitopes on human CCL2, pharmaceutical compositions thereof, their manufacture, and use as medicaments for the treatment of cancers, inflammatory, autoimmune and ophthalmologic diseases.

Abstract: Herein is reported an immunoassay for quantifying the amount of anti-drug antibody, which anti-drug antibody can specifically bind to a drug antibody, which drug antibody can specifically bind to a therapeutic target, in a serum or plasma sample comprising the steps of a) incubating the serum or plasma sample at a pH value that is about the pI value of the target, and optionally removing formed precipitate after the incubation, b) incubating the serum or plasma sample obtained in step a) at a pH value of about 2, and optionally centrifuging the incubated sample to remove formed precipitate, c) adjusting the pH value to about 7.

Abstract: Herein is reported a method for the determination of the binding affinity of a binder and its ligand comprising the step of determining based on the result of an immunoassay the fraction of free binder in a sample comprising binder, ligand and binder-ligand-complexes for at least two different binder:ligand ratios in the sample, and if the determined fraction of free binder is not comparable for all used binder:ligand ratios then the binder:ligand ratio in the sample is lowered and the sample is re-analyzed by the same immunoassay, and calculating based on the fraction of free binder in the previous step the binding affinity for the binder to its ligand.

Abstract: Herein is reported a method for determining in a sample the (total, i.e. binding competent) amount of a ligand of a ligand-binding protein (therapeutic) comprising the following steps in the following order: subjecting the sample to an acid treatment, forming in solution a non-covalent complex comprising i) an anti-ligand antibody, ii) the ligand, and iii) labelled ligand-binding protein, by adding anti-ligand antibody and labelled ligand-binding protein to the sample, and determining the amount of the complex and thereby determining the amount of the ligand of the ligand-binding protein.

Abstract: Herein is reported a method for determining in a sample the (total, i.e. binding competent) amount of a ligand of a ligand-binding protein (therapeutic) comprising the following steps in the following order: subjecting the sample to an acid treatment, forming in solution a non-covalent complex comprising i) an anti-ligand antibody, ii) the ligand, and iii) labelled ligand-binding protein, by adding anti-ligand antibody and labelled ligand-binding protein to the sample, and determining the amount of the complex and thereby determining the amount of the ligand of the ligand-binding protein.

Abstract: Thus, herein is reported a method for analyzing/characterizing circulating immune complexes (CICs) formed in vivo comprising a size-exclusion chromatography of a sample obtained from a mammal to which the drug had been administered at least once for determining the weight/size of the immune complexes, optionally a second non-SEC chromatography, and at least one immunoassay, whereby the immune complex is characterized by the correlation of the immune complex size and the immunoassay result/read-out. Also reported herein is the use of a method as reported herein for determining a correlation to altered pharmacokinetics, for determining loss or reduction of efficacy, for determining neutralization of natural counterparts of the drug, for determining immune and hypersensitivity reactions, including serum sickness/type III hypersensitivity reaction/immune complex-mediated disease.

Abstract: Herein is reported a method for the determination of the binding affinity of a binder and its ligand comprising the step of determining based on the result of an immunoassay the fraction of free binder in a sample comprising binder, ligand and binder-ligand-complexes for at least two different binder:ligand ratios in the sample, and if the determined fraction of free binder is not comparable for all used binder:ligand ratios then the binder:ligand ratio in the sample is lowered and the sample is re-analyzed by the same immunoassay, and calculating based on the fraction of free binder in the previous step the binding affinity for the binder to its ligand.