Fred Hutchinson Cancer Center

Amgen Inc.

Amgen Research (munich) Gmbh

Amgen Research Gmbh

Roland B Walter

Christopher Mehlin

Hans-Peter Kiem

Colin Correnti

Marion Subklewe

Olivier M Humbert

Christina Krupka

George S Laszlo

Christina HEITMÜLLER

Systems and methods to selectively protect therapeutic cells by reducing CD33 expression in the therapeutic cells and targeting non-therapeutic cells with an anti-CD33 therapy. The selective protection results in the enrichment of the therapeutic cells while simultaneously targeting any diseased, malignant and/or non-therapeutic CD33 expressing cells within a subject.

Reducing CD33 expression to selectively protect therapeutic cells

Anti-CD33 antibodies are described. The anti-CD33 antibodies can bind within the V-set Ig-like domain or the C2-set Ig-like domain of CD33. Epitopes FIG.A on the C2-set Ig-like domain can provide a 'pan-binding' site, to which the cognate antibody will bind regardless of whether the CD33 molecule also contains the V-set domain (as in, for example, CD33) or not (as in, for example, CD33). Alternative epitopes on the C2-set Ig-like domain are accessible for binding if the V-set domain is absent (e.g., as in CD33). Antibodies that bind an epitope on the C2-set Ig-like domain (whether they exhibit pan or V-set absent binding) are directed at novel therapeutic targets can increase therapeutic efficacy against CD-33-related disorders. Also described are molecules comprising a binding-competent domain from at least one described anti-CD33 antibody, including scFvs, bi-specific antibody molecules, chimeric antigen receptors, and immunoconjugates. Methods of use are also provided.

Anti-CD33 antibodies and uses thereof

The present invention provides a combination epigenetic factors and bispecific compounds targeting CD33 and CD3 in the treatment of myeloid leukemia, wherein the epigenetic factor is selected from the group consisting of histone deacetylase (HDAC) inhibitors, DNA methyltransferase (DNMT) I inhibitors, hydroxyurea, Granulocyte-Colony Stimulating Factor (G-CSF), histone demethylase inhibitors and ATRA (All Trans-retinoic acid). Accordingly, the invention provides a pharmaceutical composition comprising a CD33 targeting compound and at least one epigenetic factor and an epigenetic factor for use in the amelioration and/or treatment of a myeloid leukemia, wherein the epigenetic factor increases the responsiveness of a patient to a CD33 targeting compound. Moreover, the invention provides the use of at least one an epigenetic factor for increasing the responsiveness of a myeloid leukemia patient to a treatment with a CD33 targeting compound, a method for the treatment of a myeloid leukemia, the method comprising the administration of at least one epigenetic factor and a CD33 targeting compound to a patient in the need thereof and a kit comprising a pharmaceutical composition of the invention or an epigenetic factor of the invention and a bispecific CD33 targeting compound.

Combination of epigenetic factors and bispecific compounds targeting CD33 and CD3 in the treatment of myeloid leukemia

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Seattle, WA, United States of America

Roland B Walter