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Use of activatable anti-PDL1 and anti-CTLA-4 antibodies in neoassisted combination therapy for treatment of cancer

A technology of CTLA-4 and combination therapy, applied in the direction of antibody medical components, chemical instruments and methods, antibodies, etc., can solve problems such as limiting the effectiveness of therapy

Pending Publication Date: 2022-03-11
CYTOMX THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Antibody-based therapies have provided effective treatment for several diseases, but in some cases, toxicity due to broad target expression limits the therapeutic effectiveness of these therapies
In addition, antibody-based therapeutics exhibit other limitations, such as rapid clearance from circulation after administration

Method used

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  • Use of activatable anti-PDL1 and anti-CTLA-4 antibodies in neoassisted combination therapy for treatment of cancer
  • Use of activatable anti-PDL1 and anti-CTLA-4 antibodies in neoassisted combination therapy for treatment of cancer
  • Use of activatable anti-PDL1 and anti-CTLA-4 antibodies in neoassisted combination therapy for treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0156] An exemplary treatment regimen using the combination therapy described above is described in Example 1.

[0157] The activatable anti-PDL1 antibodies and anti-CTLA-4 antibodies employed in the methods of the invention can be formulated as pharmaceutical compositions suitable for intravenous administration. Each compound may be provided in lyophilized or solution form, but if either compound is provided in lyophilized form it is dissolved in a pharmaceutically acceptable diluent prior to administration. For intravenous administration, suitable diluents include physiological saline, bacteriostatic water, Cremophor EL TM (BASF, Parsippany, N.J.), phosphate-buffered saline (PBS), etc. Pharmaceutical compositions comprising activatable anti-PDL1 antibodies suitable for use in the practice of the invention are described in PCT Publication Nos. WO 2016 / 149201 and WO 2018 / 222949, each of which is incorporated herein by reference. In all cases, the composition must be sterile....

Embodiment

[0178] Activatable anti-PDL1 antibody and anti-CTLA-4 antibody as neoadjuvant combination therapy in subjects with solid tumors assessment of body composition

[0179] This study evaluates the antitumor effect of the combination of PL07-2001-C5H9v2 and ipilimumab in subjects with solid tumors based on the pathological response after neoadjuvant administration of neoadjuvant combination therapy.

[0180] PL07-2001-C5H9v2 is a protease-activatable anti-PDL1 antibody comprising the heavy chain sequence of SEQ ID NO:122 and the light chain sequence of SEQ ID NO:124. PL07-2001-C5H9v2 contains two heavy chains and two light chains. The light chain contains a prodomain sequence comprising MM and CM. See WO 2016 / 149201 and WO 2018 / 222949. The corresponding activated anti-PDL1 antibody binds human PDL1.

[0181] Ipilimumab is an anti-CTLA-4 antibody. It is a fully human IgG1 monoclonal antibody that blocks the binding of CTLA-4 to its B7 ligand and is marketed as YERVOY.

[01...

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Abstract

The present invention relates generally to the use of a novel adjuvant combination therapy that can activate an anti-PDL1 antibody with an anti-CTLA-4 antibody for the treatment of cancer.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Patent Application Serial No. 62 / 860,953, filed June 13, 2019, which is hereby incorporated by reference in its entirety. [0003] References to Sequence Listings [0004] Pursuant to Title 37 of the Code of Federal Regulations (C.F.R.) Section 1.821, the "Sequence Listing" submitted electronically in computer readable form (CFR) via EFS-Web as the file name "sequencelisting.txt" is hereby incorporated by reference This article. The electronic copy of the sequence listing was created on June 12, 2020 and has a disk capacity of 37.6 kilobytes. [0005] field of invention [0006] The present invention relates generally to the use of activatable anti-PDL1 antibodies and anti-CTLA-4 antibodies in neoadjuvant combination therapy for the treatment of cancer. [0007] Background of the invention [0008] Antibody-based therapies have provided effective treatment for se...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P35/00C07K16/28
CPCA61K39/3955A61P35/00C07K16/2827C07K16/2818A61K2039/507A61K2039/545A61K2039/876C07K2317/56C07K2317/565A61K39/001129C07K2317/21C07K2319/50
Inventor R·汉弗莱M·威尔Y·亚隆
Owner CYTOMX THERAPEUTICS
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