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Engineered polypeptides with enhanced duration of action and reduced immunogenicity

An engineering and active fragment technology, which is applied to peptides containing affinity tags, peptides containing His tags, medical preparations with non-active ingredients, etc., can solve the problem of increased duration of action and achieve the effect of improving patient compliance

Active Publication Date: 2017-10-10
AMYLIN PHARMACEUTICALS LLC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Without wishing to be bound by any theory, it is believed that because the engineered polypeptides described herein can bind albumin, the compounds can be sequestered (e.g., bound to albumin) when in circulation, due to, for example, renal clearance and / or decreased degradation resulting in increased duration of action

Method used

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  • Engineered polypeptides with enhanced duration of action and reduced immunogenicity
  • Engineered polypeptides with enhanced duration of action and reduced immunogenicity
  • Engineered polypeptides with enhanced duration of action and reduced immunogenicity

Examples

Experimental program
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preparation example Construction

[0305] The preparation method of the above-mentioned liquid preparation generally includes the steps of compounding, sterile filtration and filling. The dosing procedure involves dissolving ingredients in a specified order (preservatives, then stabilizers / tonicity agents, buffers and peptides) or simultaneously.

[0306] Alternative formulations, such as non-parenteral formulations, may not require sterilization. However, if sterilization is desired or necessary, any suitable method of sterilization can be used to develop the peptide pharmaceutical formulations of the invention. Typical sterilization methods include filtration, steam (moist heat), dry heat, gases (e.g., ethylene oxide, formaldehyde, chlorine dioxide, propylene oxide, β-propiolactone, ozone, chloropicrin, peracetic acid, methyl bromide, etc.), exposure to radioactive sources and aseptic processing. Filtration is the preferred method of sterilization of liquid formulations of the invention. Sterile filtration...

Embodiment approach 1

[0383] Embodiment 1. An engineered polypeptide comprising: an albumin binding domain polypeptide (ABD) sequence and a first peptide hormone structure selected from an exendin sequence, an exendin analog sequence, or an active fragment sequence thereof domain (HD1) sequence.

Embodiment approach 2

[0384] Embodiment 2. The engineered polypeptide of embodiment 1, further comprising a first linker (L1) covalently linking said HD1 sequence and said ABD sequence.

[0385] 3. The engineered polypeptide of embodiment 1 or 2, wherein said engineered polypeptide comprises said ABD sequence as a C-terminal portion and said HD1 sequence as an N-terminal portion

[0386] 4. The engineered polypeptide of embodiment 3, comprising the structure: HD1-ABD.

[0387] 5. The engineered polypeptide of embodiment 3, comprising the structure: HD1-L1-ABD.

[0388] 6. The engineered polypeptide of any one of embodiments 1-5, wherein said HDl sequence is said exendin or exendin analog sequence.

[0389] 7. The engineered polypeptide of embodiment 6, wherein the exendin sequence is an exendin-4 sequence and the exendin analog sequence is a Leul4 exendin-4 sequence.

[0390] 8. The engineered polypeptide of embodiment 6, wherein the exendin fragment sequence is exendin-4 (1-28), exendin-4 (1-29)...

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Abstract

Compounds with particularly good duration of action, high potency and / or convenient dosing regimens (including oral administration) and reduced immunogenicity are provided. The compounds are engineered polypeptides comprising an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treating diseases and conditions including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, short bowel syndrome, Parkinson's disease, and Cardiovascular disease.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to USSN 61 / 505982, filed July 8, 2011, and USSN 61 / 585577, filed January 11, 2012, both of which are incorporated by reference for all purposes. [0003] sequence listing [0004] This application contains a Sequence Listing, filed in ASCII format via EFS-Web, which is incorporated by reference in its entirety. Said ASCII copy was created on June 22, 2012, named 0263WO1.txt, and was 366,392 bytes in size. Background of the invention [0005] The present application relates to compounds having good duration of action, high potency, and / or convenient dosing regimens, including oral administration, and methods of use thereof. Provided herein are engineered polypeptides comprising an albumin binding domain in combination with a biologically active peptide. Without wishing to be bound by any theory, it is believed that because the engineered polypeptides described herein can bind albumin, t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K1/00C12P21/00
CPCA61K47/65A61P1/00A61P1/04A61P1/16A61P3/00A61P3/04A61P3/06A61P3/08A61P3/10A61P9/00A61P9/10A61P11/00A61P25/16A61P25/28C07K14/605C07K2319/21C07K2319/31C07K2319/50C07K2319/70
Inventor M.埃里克森D.C.利青格尔S.S.高希Z.郭M.P.萨曼特A.沙马L.马梅多瓦O.E.莱维C.埃克布拉徳
Owner AMYLIN PHARMACEUTICALS LLC