Methods for treating fibrotic cancers

Inventors

Bruhn, Suzanne • Trehu, Elizabeth • Lupher, Jr., Mark

Assignees

Promedior Inc

Abstract

In part, the disclosure relates to methods of treating fibrotic cancers by administering one or more Serum Amyloid Protein (SAP) agonists. In certain aspects, the method further comprises the conjoint administration of an anti-cancer therapeutic, e.g., a chemotherapeutic agent. In certain aspects, the disclosure relates to methods of treating myelofibrosis by administering an SAP agonist and optionally one or more anti-cancer therapeutic agents.

Core Innovation

The invention relates to treating a fibrotic cancer or improving the efficacy of an anti-cancer therapeutic in a patient having fibrotic cancer by administering a therapeutically effective amount of a serum amyloid P (SAP) agonist. The SAP agonist is an SAP polypeptide that binds to Fcγ receptors and provides an inhibitory signal to fibrocytes and fibrocyte precursors in vitro. Treatment is limited such that the fibrotic cancer is not pancreatic cancer, and eligibility includes patients in whom the efficacy of a Jak kinase inhibitor has decreased or who are unresponsive, resistant, or refractory to a JAK kinase inhibitor prior to initiation of SAP agonist treatment.

The method provides a dosing schedule including one or more times in an initial loading dose during a first week of administration followed by one time every one to four weeks. Each administration of the SAP agonist is 0.1–40 mg/kg. The invention further contemplates SAP agonist dosing as monotherapy or as improving the efficacy of an anti-cancer therapeutic through combination with one or more additional active agents.

In related refinements, the SAP agonist is characterized as glycosylated human SAP polypeptide forms with an N-linked oligosaccharide chain having terminal sialylation patterns, including at least one branch ending in a 2,3-linked sialic acid moiety and optionally being substantially free of 2,6-linked sialic acid moieties. Additional refinements specify the SAP polypeptide amino acid sequence, including a polypeptide comprising SEQ ID NO:1 and/or containing an amino acid sequence at least 95% identical to SEQ ID NO:1.

Claims Coverage

The independent claims cover four method types: SAP agonist monotherapy, SAP agonist with additional active agents, fibrotic cancer treatment with the same SAP agonist dosing structure and JAK inhibitor status eligibility, and a myelofibrosis-specific SEQ ID NO:1 SAP agonist method. The claims tie eligibility to decreased efficacy or resistance/refractoriness to a JAK kinase inhibitor and define the SAP agonist by Fcγ-receptor binding with inhibitory signaling to fibrocytes and fibrocyte precursors in vitro.

Across the independent claims, inventive coverage is centered on using an SAP polypeptide that binds to Fcγ receptors and provides an inhibitory signal to fibrocytes and fibrocyte precursors in vitro, administered with an initial loading dose in the first week followed by dosing every one to four weeks at 0.1–40 mg/kg, for fibrotic cancers excluding pancreatic cancer, in patients whose JAK kinase inhibitor efficacy has decreased or who are unresponsive, resistant, or refractory to a JAK kinase inhibitor prior to SAP agonist initiation. Additional independent-claim scope includes combination with additional active agents and a myelofibrosis embodiment using an SAP polypeptide comprising SEQ ID NO:1.

Stated Advantages

Documented Applications