Cancer models and associated methods
AssigneeNGM Biopharmaceuticals, Inc.
InventorLei LING
Life of this patent
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Abstract
Models useful in determining whether fibroblast growth factor 19 variant polypeptides having glucose-lowering activity and/or anti-obesity activity also exhibit favorable oncology-related profiles, and methods and uses associated therewith. Also provided are methods of antagonizing the oncogenic activity of FGF19 in a subject and, in certain embodiments, methods of preventing or treating a disease, disorder or condition, such as a FGF19-dependent disease, disorder or condition, or a symptom thereof.
Claims72
A method for determining whether a test subject having a metabolic disorder is a candidate for treatment with a FGF19 variant, comprising:
- (a) co-administering FGF19 or a FGF19 surrogate, and a FGF19 variant to the test subject having a metabolic disorder, wherein the amount of the FGF19 or the FGF19 surrogate administered to the test subject is sufficient to induce a cancerous condition in a reference population, and
- (b) determining whether an indicia of a cancerous condition is observed in the test subject;
- wherein the absence of an indicia of a cancerous condition indicates that the test subject is a candidate for treatment with a FGF19 variant.
A method for determining whether a test subject having a metabolic disorder is a candidate for treatment with a FGF19 variant, comprising:
- (a) providing a test subject having an indicia of a cancerous condition, the subject having a metabolic disorder, ω-administering FGF19 or a FGF19 surrogate, and a FGF19 variant to the test subject, wherein the amount of the FGF19 or the FGF19 surrogate administered to the test subject is sufficient to induce a cancerous condition in a reference population, and
- (b) determining whether an indicia of a cancerous condition is enhanced in the test subject;
- wherein the absence of enhancement of an indicia of a cancerous condition indicates that the test subject is a candidate for treatment with a FGF19 variant.
A method for determining whether a test subject having a metabolic disorder is a candidate for treatment with a FGF19 variant, comprising:
- (a) providing a test subject having an indicia of a cancerous condition, the test subject having a metabolic disorder, ω-administering FGF19 or a FGF19 surrogate, and a FGF19 variant to the test subject, wherein the amount of the FGF19 or the FGF19 surrogate is administered to the test subject is sufficient to induce a cancerous condition in a reference population, and
- (b) determining whether an indicia of a cancerous condition is reduced in the test subject;
- wherein the reduction of an indicia of a cancerous condition indicates that the test subject is a candidate for treatment with a FGF19 variant.
A method for determining whether a FGF19 variant is a candidate for treating a test subject having a metabolic disorder, comprising:
- (a) co-administering FGF19 or a FGF19 surrogate, and the FGF19 variant to the test subject having a metabolic disorder, wherein the amount of the FGF19 or the FGF19 surrogate administered to the test subject is sufficient to induce a cancerous condition in a reference population, and
- (b) determining whether an indicia of a cancerous condition is observed in the test subject;
- wherein the absence of an indicia of a cancerous condition indicates that the FGF19 variant is a candidate for treatment of the test subject.
A method for determining whether a FGF19 variant is a candidate for treating a test subject having a metabolic disorder, comprising:
- (a) providing a test subject having a metabolic disorder, the test subject having an indicia of a cancerous condition, ω-administering FGF19 or a FGF19 surrogate, and a FGF19 variant to the test subject, wherein the amount of the FGF19 or the FGF19 surrogate is administered to the test subject is sufficient to exacerbate a cancerous condition in a reference population, and
- (b) determining whether an indicia of a cancerous condition is enhanced in the test subject;
- wherein the absence of exacerbation of an indicia of a cancerous condition indicates that the FGF19 variant is a candidate for treatment of the test subject.
A model for determining whether a FGF19 variant is a candidate for preventing a cancerous disease, disorder or condition in a subject having a metabolic disorder, the model comprising a subject that i) does not exhibit an indicia of a cancerous condition prior to the administration of an effective amount of a FGF19 or a FGF19 surrogate, and ii) exhibits an indicia of a cancerous condition after the administration of the FGF19 or FGF19 surrogate;
- and wherein an indicia of a cancerous condition improves upon administration of an effective amount of a polypeptide comprising or consisting of an amino acid sequence set forth in SEQ ID NO:1.
A model for determining whether a FGF19 variant is a candidate for treating a cancerous disease, disorder or condition in a subject having a metabolic disorder, the model comprising a subject having at least one indicia of cancer resulting from administration of FGF19 or FGF19 surrogate, wherein the indicia of cancer improves upon administration of an effective amount of a polypeptide comprising or consisting of an amino acid sequence set forth in SEQ ID NO:1.
A method of antagonizing the oncogenic activity of FGF19 in a subject, comprising administering to the subject a therapeutically effective amount of a FGF19 variant, thereby antagonizing the oncogenic activity of FGF19 in the subject.
A method of treating a FGF19-dependent cancer or tumor, or a symptom thereof, in a subject, comprising administering to the subject a therapeutically effective amount of a FGF19 variant, wherein there is an improvement in the cancer, tumor or symptom thereof in the subject.
A method of preventing a FGF19-dependent cancer or tumor, or a symptom thereof, in a subject, comprising administering to the subject a therapeutically effective amount of a FGF19 variant, wherein the cancer, tumor, or symptom thereof is prevented in the subject, thereby preventing the FGF19-dependent cancer or tumor in the subject.
Dependencies are inferred from the claim text.