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Cancer models and associated methods

A cancer, disease technology, applied in the field of prevention or treatment of disease, disorder or disease or its symptoms, can solve problems such as debilitating people

Pending Publication Date: 2021-12-10
NGM BIOPHARMLS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Unfortunately, this approach is often associated with serious, often debilitating adverse effects

Method used

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  • Cancer models and associated methods
  • Cancer models and associated methods
  • Cancer models and associated methods

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 4

[0148] Example 4 illustrates the effect on body weight of mice initially measured prior to injection of the indicated transgenes and subsequently determined at 3, 5 and 23 weeks post-injection. Such as Figure 4 Depicted in , transgenic db / db mice co-expressing the FGF19 variant M70 and FGF19 exhibited significant body weight loss compared to control-dosed animals, whereas that observed in mice expressing only the FGF19 transgene The effect on body weight was not significant. The body weight changes observed in mice co-expressing the FGF19 and M70 transgenes were also reflected in reduced liver weights compared to liver weights harvested from animals in the control group.

[0149] The effect of transgene expression on blood glucose was also assessed before transgene injection and at 3, 5, and 23 weeks post-injection in a manner similar to body weight measurements. Figure 5 The results presented in demonstrate that transgenic db / db mice co-expressing the FGF19 variant M70 an...

Embodiment 2

[0309] Materials and methods for Examples 2-5

[0310] The following methods and materials were used for Examples 2-5.

[0311] animal .Under controlled light (12 hours light and 12 hours dark cycle, 6:30p.m.-6:30a.m. dark), temperature (22±4℃) and humidity (50%±20%) , db / db mice (The Jackson Laboratory, Bar Harbor, ME) (approximately 15-week-old mice and approximately 36-48 g body weight at the start of treatment) were cared for according to welfare guidelines. Mice had free access to autoclaved distilled water and ad libitum access to a commercial chow containing 1 kcal % fat, 24 kcal % protein and 58 kcal % carbohydrate (Harlan Laboratories, Indianapolis, Indiana, Irradiated 2018 Teklad Global 18% Protein Rodent Diet). All animal studies were approved by the NGM Institutional Animal Care and Use Committee.

[0312] Nucleic Acid and Amino Acid Sequences . FGF19 ORF (ORF encoding cDNA of hFGF19 (GenBank Accession No. NM_005117.2) and its encoded protein sequence (GenBa...

Embodiment 2

[0322] Plasma FGF19 levels in db / db mice after gene delivery

[0323] A 24-week study was performed to assess whether the FGF19 variant M70 could prevent FGF19-induced tumorigenesis in db / db mice. As an alternative to conventional delivery methods, AAV was used as a vehicle in this example (and subsequent examples 2-4) to deliver and express relevant exogenous genes in mice and achieve continuous, sustained, and systemic exposure to The proteins encoded by these transgenes.

[0324] Prior to gene delivery, mice were divided into six groups (5 male mice / group) as described in Table 1, and blood glucose and body weight measurements were recorded for each mouse.

[0325] Table 1

[0326]

[0327] At week 0, mice were injected with 0.2 mL of saline or 0.2 mL of one of the AAV constructs from groups 2-6. At weeks 3 and 5, blood glucose and body weight measurements were again recorded for each mouse in groups 1-6.

[0328] Five weeks after gene delivery, FGF19 concentrations ...

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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.

Description

[0001] This application is a divisional application of a Chinese invention patent application with an application date of October 27, 2014, an application number of 201480070292.4, and a title of "cancer model and related methods". [0002] Cross References to Related Applications [0003] This application claims the benefit of U.S. Serial No. 61 / 896,473, filed October 28, 2013; U.S. Serial No. 61 / 922,586, filed December 31, 2013; and U.S. Serial No. 62 / 067,273, filed October 22, 2014 , each of which is incorporated herein by reference in its entirety. technical field [0004] Among other things, the present invention relates to models that can be used to determine whether polypeptide variants of fibroblast growth factor having glucose-lowering activity also display favorable oncology-related features, and to the aforementioned methods and uses. Also provided are methods of antagonizing the oncogenic activity of FGF19 in a subject, and in certain embodiments, methods of preve...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/00
CPCG01N33/74G01N2800/04G01N2800/042G01N2800/7066A61K38/1825A61P1/04A61P1/16A61P11/00A61P13/08A61P3/04A61P35/00A61P3/10A01K67/0275C12Q1/6806A01K2227/105A01K2267/0331G01N33/5088G01N2800/7028
Inventor 雷·灵
Owner NGM BIOPHARMLS
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