Glycemic control using intrinsic factor bound to a vitamin B12 conjugate of a glucagon-like peptide-1 receptor agonist
Inventors
Doyle, Robert • Bortz, Jonathan D. • Hermelin, David S.
Assignees
XERAGENX LLC • Syracuse University
Publication Number
US-11771772-B2
Publication Date
2023-10-03
Expiration Date
2036-05-20
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Abstract
The present invention provides compositions and methods for lowering blood glucose. More specifically, the present invention provides compositions comprising a complex comprising IF and B12 conjugated to a peptide comprising a GLP-1 agonist. Advantageously, the composition may be delivered subcutaneously.
Core Innovation
The invention provides compositions and methods for lowering blood glucose by using a complex that combines intrinsic factor (IF) with vitamin B12 (B12) conjugated to a peptide comprising a glucagon-like peptide-1 (GLP-1) receptor agonist. This complex can be delivered subcutaneously or intraperitoneally to subjects in need thereof, resulting in a rapid and significant decrease in blood glucose levels.
The problem addressed by this invention is the need for GLP-1 receptor agonists with improved efficacy and pharmacokinetics, particularly due to the poor bioavailability of these peptides when administered subcutaneously. Current GLP-1 receptor agonists may display limited glycemic control when used alone or even as B12-peptide conjugates without intrinsic factor.
This invention distinguishes itself by complexing the B12-peptide conjugate with intrinsic factor before administration. Through binding of intrinsic factor to B12 conjugated GLP-1 receptor agonists, the composition achieves increased bioavailability and enhanced glucose-lowering activity compared to the conjugate alone. The invention enables the production and use of such complexes for lowering blood glucose and treating diabetes mellitus, including both type 1 and type 2 diabetes.
Claims Coverage
There is one independent claim in this patent, focusing on a method for lowering blood glucose using a specific pharmaceutical composition. The following inventive features are extracted from the claim.
Administration of intrinsic factor complexed with a B12 conjugate containing a GLP-1 receptor agonist
A method comprising subcutaneously or intraperitoneally administering to a subject an effective amount of a pharmaceutical composition. The composition contains intrinsic factor (IF) complexed with a conjugate that includes vitamin B12 or an analog of B12, which is conjugated to a peptide comprising a glucagon-like peptide-1 (GLP-1) receptor agonist.
The claim coverage centers on the specific method of using an intrinsic factor and B12-peptide conjugate complex, administered subcutaneously or intraperitoneally, to lower blood glucose.
Stated Advantages
Enables a rapid and significant drop in glucose levels following administration relative to a peptide conjugated to B12 alone.
Increases bioavailability of the GLP-1 receptor agonist when complexed with intrinsic factor compared to the peptide or B12-peptide conjugate alone.
May allow for subcutaneous delivery of GLP-1 receptor agonists with improved efficacy.
Provides a method that can mitigate the effect of TCII sequestration of a B12 conjugate after administration.
Potential mitigation of nausea side effects associated with incretin hormone use, while maintaining glucose control.
Documented Applications
Lowering blood glucose in a subject following administration of a pharmaceutical composition comprising a complex of intrinsic factor and a B12 conjugate of a GLP-1 receptor agonist.
Treatment of diabetes mellitus in subjects, including type 1 and type 2 diabetes.
Use in humans, livestock animals, companion animals, laboratory animals, and zoological animals for glycemic control.
Mitigating the effect of TCII sequestration of a B12 conjugate by complexing with intrinsic factor before administration.
Potential reduction of nausea associated with exendin-4 therapy via B12 conjugation.
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