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Il-15/il-15ra heterodimeric fc fusion proteins and uses thereof

Inactive Publication Date: 2019-12-05
XENCOR
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a method of treating cancer that reduces the amount of leakage in the patient's blood vessels and does not cause low levels of protein in the blood. This treatment can improve the effectiveness of both traditional cancer therapies and new treatments that target specific cancer cells.

Problems solved by technology

However, as potential drugs, both cytokines suffer from a very fast clearance, with half-lives measured in minutes.
IL-2 immunotherapy has been associated with systemic toxicity when administered in high doses to overcome fast clearance.
Despite the promise of checkpoint blockade therapies such as nivolumab and pembrolizumab, many patients still fail to achieve sufficient response to checkpoint blockade alone.

Method used

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  • Il-15/il-15ra heterodimeric fc fusion proteins and uses thereof
  • Il-15/il-15ra heterodimeric fc fusion proteins and uses thereof
  • Il-15/il-15ra heterodimeric fc fusion proteins and uses thereof

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[0930]Examples are provided below to illustrate the present invention. These examples are not meant to constrain the present invention to any particular application or theory of operation. For all constant region positions discussed in the present invention, numbering is according to the EU index as in Kabat (Kabat et al., 1991, Sequences of Proteins of Immunological Interest, 5th Ed., United States Public Health Service, National Institutes of Health, Bethesda, entirely incorporated by reference). Those skilled in the art of antibodies will appreciate that this convention consists of nonsequential numbering in specific regions of an immunoglobulin sequence, enabling a normalized reference to conserved positions in immunoglobulin families. Accordingly, the positions of any given immunoglobulin as defined by the EU index will not necessarily correspond to its sequential sequence.

[0931]General and specific scientific techniques are outlined in US Publications 2015 / 0307629, 2014 / 028827...

example 7

XX. Reduction in Potency does not Affect the Immune Mechanism of IL-15 / Rα-Fc Fusion Proteins

[1055]The reduced potency of XmAb24306 requires a greater concentration to achieve the same level of T cell expansion at higher potency IL-15 / Rα-Fc fusion proteins such as WT XENP20818. However, there were concerns that the reduction in potency and / or the greater concentration would alter the immune mechanism associated with IL-15 / Rα-Fc treatment. Accordingly, we investigated the profile of immune-related genes in PBMCs, isolated CD8+ T cells, and isolated NK cells following incubation with either XENP20818 (WT IL-15 / Rα-Fc fusion) and XmAb24306 at their respective EC50.

[1056]CD8+ T cells were enriched using the EasySep™ Human CD8+ T Cell Enrichment Kit (STEMCELL Technologies, Vancouver, Canada) according to the manufacturer's instructions. NK cells were enriched with EasySep™ Human CD56 Positive Selection Kit II (STEMCELL Technologies, Vancouver, Canada) according to the manufacturer's instr...

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Abstract

The present invention is directed to novel IL-15 / IL-15Rα heterodimeric Fc fusion proteins and uses thereof. The IL-15 / IL-15Rα heterodimeric Fc fusion proteins can be administered to a patient to treat cancer. In some cases, the IL-15 / IL-15Rα heterodimeric Fc fusion protein is administered in combination with a checkpoint blockage antibody such as a PD-1 antibody.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 62 / 659,563 filed Apr. 18, 2018, U.S. Provisional Application No. 62 / 684,143 filed Jun. 12, 2018, U.S. Provisional Application No. 62 / 724,396 filed Aug. 29, 2018, and U.S. Provisional Application No. 62 / 756,800, filed Nov. 7, 2018, the disclosures are incorporated by reference in their entirety.SEQUENCE LISTING[0002]The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Jun. 11, 2019, is named 067461-5203-US_SL.txt and is 561,630 bytes in size.BACKGROUND OF THE INVENTION[0003]Two very promising approaches in cancer immunotherapy include cytokine-based treatments and blockade of immune checkpoint proteins such as PD-1.[0004]Cytokines such as IL-2 and IL-15 function in aiding the proliferation and differentiation of B cells, T cells, and ...

Claims

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Application Information

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IPC IPC(8): A61K38/20A61K38/17C07K16/28A61K39/395A61P35/00
CPCA61K39/3955C07K16/2818C07K2317/24C07K2317/21A61K38/2086A61P35/00A61K38/1793A61K39/395C07K14/5443C07K14/7155C07K2317/524C07K2317/526C07K2319/00C07K2319/30C07K16/2809C07K16/2812C07K16/2815C07K16/289C07K16/2866C07K16/24C07K2317/72C07K2317/94C07K2317/71A61K2300/00A61K38/00C07K16/28
Inventor BERNETT, MATTHEWDESJARLAIS, JOHNRASHID, RUMANAVARMA, RAJATBONZON, CHRISTINE
Owner XENCOR