Leptin receptor agonist antibody for use in treating metabolic dysfunction or hypoleptinemia

A technology for metabolic function and protein blood, which is applied in the field of restoring insulin sensitivity and can solve problems such as limited efficacy

Pending Publication Date: 2020-12-04
REGENERON PHARM INC
View PDF7 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these approaches often show limited efficacy, especially in leptin-resistant individuals, and are often associated with adverse side effects

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Leptin receptor agonist antibody for use in treating metabolic dysfunction or hypoleptinemia
  • Leptin receptor agonist antibody for use in treating metabolic dysfunction or hypoleptinemia
  • Leptin receptor agonist antibody for use in treating metabolic dysfunction or hypoleptinemia

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0142] Production of Human Antibodies

[0143] Anti-LEPR antibodies of the invention may be fully human antibodies. Methods for producing monoclonal antibodies, including fully human monoclonal antibodies, are known in the art. Any such known methods may be used in the context of the present invention to prepare human antibodies that specifically bind to human LEPR.

[0144] Use e.g. VELOCIMMUNE TM technology, or any other similar known method for producing fully human monoclonal antibodies, initially isolates high affinity chimeric antibodies to LEPR having human variable regions and mouse constant regions. Antibodies are characterized and selected for desired characteristics, including affinity, ligand blocking activity, selectivity, epitope, etc., as described in the Experimental section below. Fully human anti-LEPR antibodies are generated by replacing the mouse constant regions, if desired, with the desired human constant regions (eg, wild-type or modified IgGl or IgG4...

Embodiment 1

[0205] Example 1. Generation of Antigen Binding Proteins that Specifically Bind Leptin Receptor (LEPR)

[0206] by immunization with an immunogen comprising the extracellular domain of LEPR Mice (ie, mice engineered to contain DNA encoding human immunoglobulin heavy chain and kappa light chain variable regions) were used to obtain anti-LEPR antibodies. Antibody immune responses were monitored by LEPR-specific immunoassays. Fully human anti-LEPR antibodies were isolated and purified using previously described techniques.

[0207] Certain biological properties of exemplary anti-LEPR antibodies produced according to the methods of this example are described in detail in the Examples presented below.

Embodiment 2

[0208] Example 2. Heavy and light chain variable region amino acid and nucleic acid sequences

[0209] Table 1 shows the amino acid sequence identifiers of the heavy and light chain variable regions and CDRs of selected anti-LEPR antibodies of the invention. Table 2 shows the corresponding nucleic acid sequence identifiers.

[0210] Table 1: Amino Acid Sequence Identifiers

[0211]

[0212]

[0213] Table 2: Nucleic acid sequence identifiers

[0214]

[0215]Antibodies are generally referred to herein according to the following nomenclature: an Fc prefix (eg, "H4H", "H1M", "H2M", etc.), followed by a numerical identifier (eg, "16650", "16679", etc.), followed by a "P" or "N" suffix. Accordingly, according to this nomenclature, antibodies may be referred to herein, for example, as "H4H16650P2", "H4H16679P2", etc. The Fc prefix (H4H, H1M, and H2M) on antibody names as used herein indicates the specific Fc region isotype of the antibody. For example, an "H4H" antibo...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

Provided herein are therapeutic methods of treatment using agonist leptin receptor (LEPR) antibodies, antigen-binding fragments thereof, or compositions comprising the LEPR antibodies or antigen-binding fragments thereof. Such therapeutic methods include treatment for conditions related to metabolic dysfunction, including for example, lipodystrophy, adiposity or obesity, reducing body weight, non-alcoholic fatty liver disease, hyperphagia, hyperglycemia, insulin resistance, dyslipidemia, hepatic steatosis, and infertility.

Description

technical field [0001] The present invention relates to therapeutic methods for treating metabolic dysfunction and restoring insulin sensitivity in leptin deficiency and lipodystrophy using agonist antibodies and antigen-binding fragments of agonist antibodies that bind the human leptin receptor (LEPR). [0002] sequence listing [0003] The official copy of the sequence listing is submitted electronically via EFS-Web at the same time as the sequence listing in ASCII format, with the file name 10436WO_SEQ_LIST_ST25, the date of creation is April 5, 2019, and the size is about 105 kilobytes. The Sequence Listing contained in this document in ASCII format is part of the specification and is hereby incorporated by reference in its entirety. Background technique [0004] Leptin is a polypeptide hormone mainly expressed by adipose tissue that is involved in the regulation of metabolism, neuroendocrine function, immunity, energy balance and food intake. Leptin activity is mediat...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P3/00A61P3/04A61P3/10
CPCC07K16/2869A61K2039/505A61P3/00A61P3/06C07K2317/75C07K2317/92C07K2317/21C07K2317/34A61K39/3955A61K2039/54A61K2039/545A61K45/06A61K9/0019A61P3/04A61P3/10C07K2317/33C07K2317/565C07K2317/76C07K2317/94A61P15/00
Inventor J·科洛马达P·史蒂维斯J·阿尔塔雷霍斯A·J·莫菲
Owner REGENERON PHARM INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap