Interleukin-10 antibodies

Abstract

The methods and compositions provided herein relate generally to IL-10 specific antibodies and uses thereof. More specifically, compositions of humanized IL-10 specific antibodies and methods to use such antibodies in modulating the biological activity of IL-10, particularly in autoimmune disorders and pathogen-mediated immunopathology.

Description

[0001] This application claims benefit from U.S. provisional Patent Application No. 60 / 518,999, filed Nov. 10, 2003.FIELD OF THE INVENTION [0002] The present invention relates generally to interleukin-10 (IL-10) specific antibodies and uses thereof. More specifically, the invention relates to humanized antibodies that recognize human IL-10 and modulate its activity, particularly in autoimmune disorders. BACKGROUND OF THE INVENTION [0003] Initially known as cytokine synthesis inhibitor factor or CSIF, interleukin-10 (IL-10) is a potent immunomodulator of hematopoietic cells, particularly immune cells. Cells such as activated Th2 cells, B cells, keratinocytes, monocytes and macrophages produce IL-10. See, e.g., Moore et al., Annu. Rev. Immunol. 11:165 (1993). IL-10 inhibits activation and effector functions of a number of cells that include T cells, monocytes and macrophages. In particular, IL-10 inhibits cytokine synthesis, including that of IL-1, IFN-γ, and TNF, by cells such as Th1...

AI Technical Summary

Problems solved by technology

Although effective, these therapies are non-specific and substantial toxicities exist which prevent long term therapy.

The most significant limitation in using antibodies as a therapeutic agent in vivo is the immunogenicity of the antibodies.

Such an immune response results in a loss of therapeutic efficacy at a minimum and a potential fatal anaphylactic response at a maximum.

However, mice injected with hybrids of human variable regions and mouse constant regions develop a strong anti-antibody response directed against the human variable region, suggesting that the retention of the entire rodent Fv region in such chimeric antibodies may still result in unwanted immunogenicity in patients.

However, CDR loop exchanges still do not uniformly result in an antibody with the same binding properties as the antibody of origin.

While the use of CDR grafting and framework residue preservation in a number of humanized antibody constructs has been reported, it is difficult to predict if a particular sequence will result in the antibody with the desired binding, and sometimes biological, properties.

Moreover, most prior studies used different human sequences for animal light and heavy variable sequences, rendering the predictive nature of such studies questionable.

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