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Modified N-810 and methods thereof

A PD-L1, domain technology, applied in chemical instruments and methods, botanical equipment and methods, biochemical equipment and methods, etc.

Pending Publication Date: 2022-07-22
NANTBIOSCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, despite demonstrating the effectiveness of this method in vitro, biochemical analysis of the resulting protein demonstrated extensive glycosylation and heterogeneity in the final product, making industrial commercialization and regulatory approval of this biochemical would take unnecessary risks

Method used

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  • Modified N-810 and methods thereof
  • Modified N-810 and methods thereof
  • Modified N-810 and methods thereof

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Embodiment Construction

[0022] The inventors have now discovered that although multispecific protein complexes based on IL-15, such as N-803, TxM, modified N-803 or modified TxM (as in US Publication No. US 20200002425A1, incorporated herein by reference) disclosed) enhances the activity of immune cells and promotes their activity against diseased cells, resulting in the reduction or prevention of disease, but suffers from disadvantages. Throughout this disclosure, "TxM" refers to a complex comprising an IL-15N72D:IL-15RαSu / Fc scaffold linked to a binding domain. An exemplary TxM is the IL-15N72D:IL-15RαSu / Fc complex comprising a fusion to a binding domain that specifically recognizes PD-L1 (PD-L1TxM).

[0023] US Publication No. US 20200002425 A1 discloses a TxM scaffold that includes an extracellular domain of a TGF-beta receptor (eg, a "TGF-beta trap") to further functionalize the resulting protein to interact with native TGF-beta receptor competition. However, despite demonstrating the effectiv...

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Abstract

Compositions and methods for multispecific protein complexes comprising: an interleukin-15 (IL-15) domain (IL-15N72D) comprising a mutation of N72D, an IL-15 receptor [alpha] suhi-binding domain (IL-15R [alpha] Su), an immunoglobulin Fc domain, and a mutated transforming growth factor-[beta] receptor type 2 (TGF [beta] RII) domain, wherein the mutated TGF [beta] RII domain has N-> Q mutations at positions 47, 71 and 131, respectively. The IL-15R [alpha] Su structural domain, the Fc structural domain and the mutant TGF [beta] RII structural domain are sequentially connected through amido bonds. Preferably, the complexes contemplated further comprise a binding domain that specifically binds to a disease antigen, an immune checkpoint molecule or an immune signaling molecule.

Description

[0001] This application claims priority to our co-pending US Provisional Patent Application Serial No. 62 / 893,662, filed on August 29, 2019, and is incorporated herein by reference. [0002] sequence listing [0003] The contents of the ASCII text file of the Sequence Listing of size 134 kb named 102719.0021PCT_ST25 was created on August 20, 2020 and is electronically filed with this application via EFS-Web and is hereby incorporated by reference in its entirety. technical field [0004] The field of the invention is multispecific protein complexes useful in the treatment of tumors or infectious diseases. Background technique [0005] The background description includes information that can be used to understand the invention. There is no admission that any of the information provided herein is prior art or related to the presently claimed invention, nor is any publication specifically or implicitly cited to be prior art. [0006] All publications and patent applications ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00C12N15/861A61K38/20A61K38/17A61K47/68A61K45/06A61P35/00A61P31/00
CPCC07K14/5443C07K14/7155C07K14/71C07K16/2827A61K45/06A61K47/6811A61K47/6813A61P35/00A61P31/00C07K2319/30C07K2319/33C12N2710/10343C12N2800/107A61K38/00C07K2317/622C07K2319/00C07K14/495C07K2319/02C07K2319/03C12N15/63C07K14/54
Inventor 卡伊万·尼亚兹希瑟·麦克法兰
Owner NANTBIOSCI
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