B-cell reduction using cd37-specific and cd20-specific binding molecules

Abstract

The present invention generally provides methods for B-cell reduction in an individual using CD37-specific binding molecules. In particular, the invention provides methods for B-cell reduction using CD37-specific binding molecules alone, or a combination of CD37-specific binding molecules and CD20-specific binding molecules, in some instances a synergistic combination. The invention further provides materials and methods for treatment of diseases involving aberrant B-cell activity. In addition, the invention provides humanized CD37-specific binding molecules.

Description

[0001]The present application is a continuation of U.S. patent application Ser. No. 11 / 493,132, filed Jul. 25, 2006, now pending, which claims benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 60 / 702,499, filed Jul. 25, 2005, and U.S. Provisional Application No. 60 / 800,595, filed May 16, 2006. All of the above-noted applications are incorporated herein by reference in their entireties.STATEMENT REGARDING SEQUENCE LISTING[0002]The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing is 910180—404C1_SEQUENCE_LISTING.txt. The text file is 226 KB, was created on May 7, 2009, and is being submitted electronically via EFS-Web, concurrent with the filing of the specification.FIELD OF THE INVENTION[0003]The present invention generally provides methods for B-cell reduction in an individual using CD37-spec...

AI Technical Summary

Benefits of technology

[0032]“Treatment” or “treating” refers to either a therapeutic treatment or prophylactic / preventative treatment. A therapeutic treatment may improve at least one symptom of disease in an individual receiving treatment or may delay worsening of a progressive disease in an individual, or prevent onset of additional associated diseases.

[0041]Systemic Lupus Erythematosus (SLE) is an autoimmune disease caused by recurrent injuries to blood vessels in multiple organs, including the kidney, skin, and joints. In patients with SLE, a faulty interaction between T cells and B-cells results in the production of autoantibodies that attack the cell nucleus. There is general agreement that autoantibodies are responsible for SLE, so new therapies that deplete the B-cell lineage, allowing the immune system to reset as new B-cells are generated from precursors, would offer hope for long lasting benefit in SLE patients.

[0087]A “synergistic combination” of CD37-specific binding molecules and CD20-specific binding molecules is a combination that has an effect that is greater than the sum of the effects of the binding molecules when administered alone.

[0100]In addition, the properties of hydrophilicity and hydrophobicity of the compositions contemplated for use in the invention are well balanced, thereby enhancing their utility for both in vitro and especially in vivo uses, while other compositions lacking such balance are of substantially less utility. Specifically, compositions contemplated for use in the invention have an appropriate degree of solubility in aqueous media which permits absorption and bioavailability in the body, while also having a degree of solubility in lipids which permits the compounds to traverse the cell membrane to a putative site of action. Thus, antibody compositions contemplated are maximally effective when they can be delivered to the site of target antigen activity.

Problems solved by technology

In some of these methods, the combinations are synergistic.

For example, aberrant B-cell activity may include inappropriate proliferation of cells whose DNA or other cellular components have become damaged or defective.

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