Amgen Research (munich) Gmbh

Micromet Ag

Amgen Research Gmbh

Dirk Nagorsen

Gerhard Zugmaier

Juergen Scheele

Peter Kufer

Patrick Hoffmann

Matthias Klinger

Virginie Naegele

Elaine-Pashupati Dopfer

Patrick A Baeuerle

Patrick Bäuerle

Patrick Baeuerle

The present invention relates to a glucocorticoid (GC) for use in the amelioration, treatment or prophylaxis of neurological/psychiatric adverse events caused by a CD3 binding domain. Kits comprising a GC, a CD3 binding domain and instructions for use which indicate that the GC is to be employed for the treatment amelioration and/or prophylaxis of neurological adverse events caused by said CD3 binding domain, are also disclosed.

Prevention of adverse effects caused by CD3 specific binding domains

A method for assessing the risk of potential adverse effects for a human patient receiving is provided. The method comprises determining the total B count in the patient, and identifying a B cell number indicative of a patient at risk of potential adverse effects from the antibody. The method further provides a dosing schedule for administering the antibody to the patient identified as at risk of potential adverse effects. Also provided is a pharmaceutical package or kit comprising a first dose and a second dose, and optionally a third dose, the CD19&#xd7;CD3 bispecific antibody as defined in the methods/dosage regimen of the disclosure.

Dosage regimen for administering a CD19xCD3 bispecific antibody to patients at risk for potential adverse effects

The present invention relates in essence to a compound which decreases or inhibits the binding of mammalian T-cells to mammalian endothelial cells for use in a method of prophylaxis and/or amelioration and/or treatment of clinical adverse events caused by therapy which comprises re-directing of T-cells against target cells in a patient. Methods of treatment of patients having or being at risk of clinical adverse events caused by therapy which comprises re-directing of T-cells against target cells are also contemplated.

Anti-leukocyte adhesion for the mitigation of potential adverse events caused by CD3-specific binding domains

The present invention provides means and methods for treating diffuse large B cell lymphoma (DLBCL). Specifically, a bispecific CD19&#xd7;CD3 antibody which engages T cells via its CD3 binding portion and concomitantly binds to CD19 on the surface of, in particular, lymphoma cells via its CD19 binding portion (i.e. a bispecific T cell engager, 'BiTE') is administered for use in the treatment of tumorous mass of lymophoreticular tissue and/or extranodal lymphoma caused by DLBCL in a patient.

Means and methods for treating DLBCL

The disclosure provides a method for assessing the risk of potential adverse effects for a human patient mediated by the administration of a CD19&#xd7;CD3 bispecific antibody to said patient comprising determining the ratio of B cells to T cells of said patient. The disclosure also provides a method for administering a CD19&#xd7;CD3 bispecific antibody to a human patient having a B:T cell ratio of about 1:5 or lower, comprising administering doses in a dosing regimen. This dosing regimen can be applied in methods for treating malignant CD19 positive lymphocytes or for ameliorating and/or preventing an adverse effect mediated by the administration of said bispecific antibody. The Also provided is a pharmaceutical package or kit comprising a first dose and a second dose and optionally a third dose of said antibody.

Dosage regimen for administering a CD19XCD3 bispecific antibody

A method for assessing the risk of potential adverse effects for a human patient receiving a CD19&#xd7;CD3 bispecific antibody is provided. The method comprises determining the total B count in the patient, and identifying a B cell number indicative of a patient at risk of potential adverse effects from the antibody. The method further provides a dosing schedule for administering the antibody to the patient identified as at risk of potential adverse effects. Also provided is a pharmaceutical package or kit comprising a first dose and a second dose, and optionally a third dose, of the CD19&#xd7;CD3 bispecific antibody as defined in the methods/dosage regimen of the disclosure.

Dosage regimen for administrating a CD19&#xd7;CD3 bispecific antibody to patients at risk for potential adverse effects

The present invention relates in essence to use of a compound, which decreases or inhibits the binding of mammalian T-cells to mammalian endothelial cells for use in a method of prophylaxis and/or amelioration and/or treatment of clinical adverse events caused by a therapy which comprises re-directing of T-cells against target cells in a patient. Such a therapy includes, but is not limited to, treatment with an antibody comprising a CD3 binding domain, such as a CD20&#xd7;CD3 or a CD19&#xd7;CD3 bispecific single chain antibody, e.g., blinatumomab (MT-103). Methods of treatment of patients having or being at risk of clinical adverse events caused by therapy which comprises re-directing of T-cells against target cells are also contemplated, as are methods of identifying a compound for administration in the methods of prophylaxis, amelioration and/or treatment. Such anti-adhesive type compounds include, but are not limited to, antibodies, like natalizumab, efalizumab, and etrolizumab; minocycline, (acetyl-)salicyclic acid, astilbin, and flavonoids; and thrombin and pentosanpolysulfate (PPS), or a pharmaceutically acceptable salt thereof.

The present invention relates to a pentosanpolysulfate (PPS) or a pharmaceutically acceptable salt thereof for use in the amelioration, treatment, or prevention of adverse neurological events caused by administering an antibody or fragment thereof comprising a CD3 binding domain, including a CD19 x CD3 bispecific single chain antibody, such as blinatumomab. PPS is a semi-synthetically produced heparin-like macromolecular carbohydrate derivative, which chemically and structurally resembles glycosaminoglycans. Kits comprising a PPS, an antibody or fragment thereof comprising a CD3 binding domain, and instructions for administration, which indicate that the PPS is to be employed for the amelioration, treatment or prevention of adverse neurological events caused by administering the antibody or fragment thereof comprising said CD3 binding domain, are also disclosed.

PPS for the prevention of potential adverse effects caused by CD3 specific binding domains

The present invention provides means and methods for treating diffuse large B cell lymphoma (DLBCL). Specifically, a bispecific CD19&#xd7;CD3 antibody which engages T cells via its CD3 binding portion and concomitantly binds to CD19 on the surface of in particular, lymphoma cells via its CD19 binding portion (i.e. a bispecific T cell engager, 'BiTE') is administered for use in the treatment of tumorous mass of lymophoreticular tissue and/or extranodal lymphoma caused by DLBCL in a patient.

Provided herein is a method for assessing the risk of potential adverse effects for a human patient mediated by the administration of a CD19.times.CD3 bispecific antibody to said patient comprising determining the ratio of B cells to T cells of said patient, wherein a ratio of about 1:5 or lower is indicative for a risk of potential adverse effects for said patient.

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Munich, Germany

Dirk Nagorsen