Methods and compositions for the treatment of pancreatic cancer
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Publication Number
US-10047164-B2
Publication Date
2018-08-14
Expiration Date
Abstract
A composition comprising a TLR2 antagonistic antibody or antigen binding fragment thereof for use in the treatment or prophylaxis of pancreatic cancer is provided. The antibody or antigen binding fragment may be provided for simultaneous, separate or sequential administration with a secondary chemotherapeutic agent such as gemcitabine, and optionally a tertiary chemotherapeutic agent such as abraxane for enhanced treatment. Also provided is a screening method for the identification of compounds for use in treatment or prevention of pancreatic cancer.
Core Innovation
The document describes methods for treating or preventing pancreatic cancer by administering a therapeutically effective amount of a Toll-like receptor 2 (TLR2) antagonist to a subject in need thereof. The TLR2 antagonist is an antibody that specifically binds to TLR2, or an antigen binding fragment thereof.
The TLR2 antagonistic antibody is defined by binding specificity to TLR2 and by antibody structural elements, including complementarity determining regions (CDRs) and SEQ ID-described variable regions. In the disclosed examples, embodiments include humanized anti-TLR2 antibody T2.5, and antibody/fragment formats characterized by specified heavy-chain and light-chain variable region compositions.
The document further describes antagonizing TLR2 function independently of CD32 binding, and includes embodiments for combining the TLR2 antagonist antibody or antigen binding fragment with additional therapeutic agents in pancreatic cancer. In the described combination settings, chemotherapy regimens such as gemcitabine and optionally Abraxane are used, and the document characterizes the resulting therapeutic effects in preclinical models.
Claims Coverage
The document contains one independent method claim, directed to administering a TLR2 antagonist antibody or antigen-binding fragment to treat or prevent pancreatic cancer, with multiple dependent claims refining the antibody identity/structure and specifying additional combination-treatment features. The independent claim is supported by dependent inventive features focused on antibody specificity and defined structural/functional constraints, plus combination-treatment options.
Administering a TLR2 antagonist antibody for pancreatic cancer treatment or prevention
A method for treating or preventing pancreatic cancer comprising administering a therapeutically effective amount of a Toll-like receptor 2 (TLR2) antagonist to a subject in need thereof, wherein the TLR2 antagonist is an antibody that specifically binds to TLR2, or an antigen binding fragment thereof.
CDR- and SEQ ID-defined antibody binding-site composition
The method wherein the antibody, or an antigen-binding fragment thereof, has heavy- and light-chain variable regions comprising specified CDR1, CDR2, and CDR3 amino-acid sequences identified by SEQ ID NOs.
SEQ ID-defined heavy- and light-chain variable regions with identity constraints
The method wherein the antibody includes a heavy chain matching SEQ ID NO:13 (or at least 90% identical) and a light chain matching SEQ ID NO:12 (or at least 90% identical), or antigen-binding fragments thereof.
TLR2 antagonism independent of CD32 binding
The method wherein the antibody (or its antigen-binding fragment) antagonizes TLR2 function independently of its binding to CD32.
Humanized anti-TLR2 antibody T2.5
The method wherein the antibody is a humanised version of the anti-TLR2 antibody T2.5, or an antigen-binding fragment thereof.
Combination administration with gemcitabine and Abraxane
The method wherein the antibody or an antigen-binding fragment, gemcitabine, and abraxane are administered simultaneously.
Overall claim coverage centers on pancreatic cancer treatment or prevention by administering a therapeutically effective amount of a TLR2 antagonistic antibody (or antigen-binding fragment) that specifically binds TLR2. Dependent claim features further specify CDR and SEQ ID-described variable region compositions (including identity constraints), require TLR2 antagonism independent of CD32 binding, include embodiments using humanized anti-TLR2 antibody T2.5, and define combination-treatment administration with gemcitabine and Abraxane.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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