Antitumor peptide derived from a complementarity determining region of a humanized monoclonal antibody to NAP12B transporter

Inventors

Travassos, Luiz Rodolpho Raja Gabaglia

Assignees

Recepta Biopharma SA

Abstract

Described herein is novel isolated or synthetic peptides derived from a complementarity determining region hypervariable domain amino acid sequence of a humanized monoclonal antibody to NaPi2B transporter, as well as derivatives thereof, and a pharmaceutical composition and a method for inhibiting tumor growth or treating a tumor or cancer treating using the antitumor peptides and derivatives thereof.

Core Innovation

The disclosure describes antitumor peptides derived from the complementarity determining region (CDR) hypervariable domain of the humanized monoclonal antibody huMX35/RebMab200 that targets NaPi2B. The peptides include CDR H3 hypervariable domain–derived sequences, including SEQ ID NO: 3 as RB10a and SEQ ID NOs: 8–9 as extended CDR H3 peptides RB9/RB10, as well as peptide derivatives including cyclic peptide variants and further modified peptides.

The antitumor peptides are positioned as agents that increase tumor cell adherence in a dose-dependent manner while inhibiting migration and invasion. The described effects include inhibition of migration using wound healing and inhibition of invasion using Matrigel transwell assays, and the disclosure further reports reduced metastatic lung colonization in a murine melanoma model and selective effects across multiple tumor cell lines.

The disclosure also describes pharmaceutical compositions comprising these antitumor peptides and a pharmaceutically acceptable carrier or diluent, including formulation into dosage forms. Peptide stability and pharmacokinetic considerations are discussed, including plasma degradation/half-life measurements, and the disclosure further reports toxicity observations including minimal observed toxicity and non-hemolytic activity.

Claims Coverage

The patent includes two independent claims that cover administering a pharmaceutical composition containing specific CDR-hypervariable-domain–derived antitumor peptides to treat tumors or inhibit tumor growth, and manufacturing that pharmaceutical composition by mixing, sterilizing, and formulating into multiple dosage forms. Across these independent claims, the core inventive features involve defined peptide selections and the combination/formulation with a pharmaceutically acceptable carrier and selected dosage form processing steps.

Overall, the claim coverage centers on treating or inhibiting tumor/cancer growth by administering an effective amount of a pharmaceutical composition containing antitumor peptides selected from specified SEQ ID NOs, and on a corresponding manufacture method that mixes the selected antitumor peptide with excipients or carriers, sterilizes, and formulates into multiple dosage forms.

Stated Advantages

Documented Applications