RP182 compositions and methods
AssigneeNantBio, Inc.
InventorsPatrick Soon-Shiong, Kayvan Niazi
Life of this patent
Estimating the term…
Abstract
Compositions and methods for domain-specific targeting of CD206 are presented in which selected agents bind to the carbohydrate recognition domain 4 (CRD4) and carbohydrate recognition domain 5 (CRD5) of CD206. In certain aspects of the inventive subject matter, binding is specific, leads to a conformational change of CD206, and will induce phagocytosis in tumor associated macrophages and/or M2 macrophage cell death.
Claims10
A method of producing a pharmaceutical agent, comprising:
- identifying a synthetic peptide as a selective binder to carbohydrate recognition domain 4 (CRD4) and carbohydrate recognition domain 5 (CRD5) of CD206;
- quantifying an affinity of the synthetic peptide to the carbohydrate recognition domain 4 (CRD4) and carbohydrate recognition domain 5 (CRD5) of CD206;
- evaluating a variant of a fragment of the synthetic peptide to establish an amino acid substitution;
- preparing a modified synthetic peptide to include the amino acid substitute to thereby produce the pharmaceutical agent, wherein substituting the amino acid increases the affinity to the carbohydrate recognition domain 4 (CRD4) and carbohydrate recognition domain 5 (CRD5) of CD206;
- and
- contacting a plurality of macrophages with the modified synthetic peptide that includes the amino acid substitute, thereby inducing phagocytic activity and/or inducing of apoptosis in M2 macrophages;
- and
- wherein the pharmaceutical agent is an RP182 analog selected from the group consisting of SEQ ID NO:2-SEQ ID NO:28.
A method of shifting a M1/M2 population of macrophages to a population with depleted M2 macrophage content, comprising:
- contacting the M1/M2 population of macrophages with a pharmaceutical agent that targets carbohydrate recognition domain 4 (CRD4) and carbohydrate recognition domain 5 (CRD5) in an amount effective to shift the M1/M2 population of macrophages to the population with depleted M2 macrophage content,
- wherein the pharmaceutical agent is an RP182 analog selected from the group consisting of SEQ ID NO:2-SEQ ID NO:28.
A method of activating phagocytosis of tumor associated macrophages, comprising:
- contacting the tumor associated macrophages with a pharmaceutical agent that targets carbohydrate recognition domain 4 (CRD4) and carbohydrate recognition domain 5 (CRD5) in an amount effective to activate phagocytosis of tumor associated macrophages,
- wherein the pharmaceutical agent is an RP182 analog selected from the group consisting of SEQ ID NO:2-SEQ ID NO:28.
Dependencies are inferred from the claim text.