IP Library › Granted Patent US 12,721,897
Granted Patent B2
US 12,721,897 · App. 18/501,061 · Granted Sep 1, 2026

Pharmaceutical compositions of polypeptide conjugates and methods of uses thereof

Inventors: Yuanyuan Zhang (Beijing, CN); Hongyu Shi (Beijing, CN); Xiaona Dong (Beijing, CN); Peng Zhai (Beijing, CN); Hongzhou Dong (Beijing, CN)
Assignee: BEIJING QL BIOPHARMACEUTICAL CO., LTD.
A61K47/542A61K9/2013A61K9/2027A61K9/2054A61K38/26A61P3/04A61P25/28
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Quick Facts
Patent No.
US 12,721,897
App. No.
18/501,061
Granted
Sep 1, 2026
Kind
B2
Abstract

The present disclosure provides polypeptide conjugates comprising GLP-1 receptor agonist and a peptide linker, and pharmaceutical compositions comprising the same. Methods of using such for treating diseases are also provided.

Claims (27)

1 . A pharmaceutical composition comprising a polypeptide conjugate and an absorption enhancing excipient, wherein:

the polypeptide conjugate comprises a polypeptide portion and one clearance-reducing moiety (CRM) conjugated to a lysine (K) residue on the polypeptide portion, wherein the polypeptide portion comprises the amino acid sequence of SEQ ID NO: 52, 55, 56, 60, 61, or 62:

wherein the CRM has the structure of below formula:

wherein “*” represents the point of attachment to a reactive group of the lysine residue on the polypeptide portion:

wherein the absorption enhancing excipient comprises sodium N-(8-(2-hydroxybenzoyl) amino) caprylic acid (SNAC); and

wherein the pharmaceutical composition is a unit dosage form comprising approximately 0.5-50 mg of the polypeptide conjugate, approximately 50-300 mg of SNAC, and approximately 1-10 mg magnesium stearate.

2 . The pharmaceutical composition of claim 1 , wherein the unit dosage form comprises:

a) approximately 0.5-10 mg of the polypeptide conjugate, approximately 50-300 mg of SNAC, and approximately 1-10 mg magnesium stearate;

b) approximately 10-20 mg of the polypeptide conjugate, approximately 100-300 mg of SNAC, and approximately 1-10 mg magnesium stearate; or

c) approximately 20-50 mg of the polypeptide conjugate, approximately 200-300 mg of SNAC, and approximately 1-10 mg magnesium stearate.

3 . The pharmaceutical composition of claim 1 , wherein the polypeptide conjugate comprises SEQ ID NO: 52 or 60 and has one of the structures shown below:

4 . A pharmaceutical composition comprising a polypeptide conjugate and an absorption enhancing excipient, wherein:

the polypeptide conjugate comprises a polypeptide portion and two clearance-reducing moieties (CRM) conjugated to lysine (K) residues on the polypeptide portion, wherein the polypeptide portion comprises the amino acid sequence of SEQ ID NO: 51, 53, 54, 57, 58, 59, 85, or 86;

wherein the CRM has the structure of below formula:

wherein “*” represents the point of attachment to a reactive group of the lysine residue on the polypeptide portion:

wherein the absorption enhancing excipient comprises SNAC; and

wherein the pharmaceutical composition is a unit dosage form comprising approximately 10-100 mg of the polypeptide conjugate, approximately 100-500 mg of SNAC, and approximately 1-20 mg magnesium stearate.

5 . The pharmaceutical composition of claim 4 , wherein the unit dosage form comprises:

a) approximately 10-20 mg of the polypeptide conjugate, approximately 100-300 mg of SNAC, and approximately 1-20 mg magnesium stearate;

b) approximately 20-40 mg of the polypeptide conjugate, approximately 200-300 mg of SNAC, and approximately 1-20 mg magnesium stearate;

c) approximately 20-50 mg of the polypeptide conjugate, approximately 200-300 mg of SNAC, and approximately 1-20 mg magnesium stearate;

d) approximately 40-50 mg of the polypeptide conjugate, approximately 200-300 mg of SNAC, and approximately 1-20 mg magnesium stearate; or

e) approximately 50-100 mg of the polypeptide conjugate, approximately 300-500 mg of SNAC, and approximately 1-20 mg magnesium stearate.

6 . The pharmaceutical composition of claim 4 , wherein the polypeptide conjugate comprises SEQ ID NO: 57 and has the structure shown below:

7 . A method of treating a metabolic disorder in a subject in need thereof, wherein the method comprises administering to the subject the pharmaceutical composition of claim 1 , and wherein the metabolic disorder is diabetes, obesity, overweight, non-alcoholic steatohepatitis (NASH), dyslipidemia, atherosclerosis, alcoholic steatohepatitis (ASH), diabetic nephropathy, gestational diabetes, metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), end-stage liver disease, hepatic steatosis, liver cirrhosis, primary biliary cirrhosis (PBC), or Alzheimer's disease.

8 . The method of claim 7 , wherein the diabetes is one or more conditions selected from the group consisting of hyperglycemia, type 2 diabetes, impaired glucose tolerance, type 1 diabetes, non-insulin dependent diabetes, maturity onset diabetes of the young (MODY), gestational diabetes, and elevated level of hemoglobin A1C (HbA1c).

9 . A method of managing body weight or reducing food intake or reducing body weight in a subject in need thereof, wherein the method comprises administering to the subject the pharmaceutical composition of claim 1 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 7, 2023
From: ZHANG, YUANYUAN; SHI, HONGYU; DONG, XIAONA; ZHAI, PENG; DONG, HONGZHOU
To: BEIJING QL BIOPHARMACEUTICAL CO., LTD.
Reel/Frame 065476/0340 →
Priority Claims (2)
WO PCT/CN2022/083026 · Mar 25, 2022 · international
WO PCT/CN2023/083257 · Mar 23, 2023 · international
Continuity (2)
Continuation PCTCN2023084208 · Mar 27, 2023
Related Publication 20240173416A1 · May 30, 2024
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