MODIFIED THERAPEUTIC AGENTS AND COMPOSITIONS THEREOF

• US 20190328888A1
• Filed: 05/07/2019
• Published: 10/31/2019
• Est. Priority Date: 09/13/2013
• Status: Active Grant

• Current Assignee: The Scripps Research Institute
• Original Assignee: The Scripps Research Institute
• Inventors: SHEN, Weijun, SCHULTZ, Peter G., MUPPIDI, Avinash, AHMAD, Insha, YANG, Pengyu
• Granted Patent: US 10,987,427 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/2221 Relaxins
• CPC Class Codes: A61K 38/2264 Obesity-gene products, e.g. leptin
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/54 the modifying agent being an organic compound
• CPC Class Codes: A61K 47/543 Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
• CPC Class Codes: A61K 47/554 the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

Methods and compositions are provided for extending the half-life of a therapeutic agent. One or more half-life extending moieties may be attached to a therapeutic agent, thereby extending the half life of the therapeutic agent. The modified therapeutic agents (mTAs) comprising one or more half-life extending moieties attached to a therapeutic agent may be used to treat a disease or condition in a subject in need thereof.

Claims

1-20. -20. (canceled)

21. A lipid conjugate (LC), comprising

a. one or more lipids, the lipids selected from a group consisting of sterols, bile acids, vitamin E, fatty di-acids, fatty acids, fatty amides, fatty amines, fatty alcohols, and derivatives thereof;

and

b. a therapeutic agent (TA) comprising an amino acid sequence that is at least about 95% homologous to SEQ ID NO;

45;

wherein the one or more lipids are conjugated to the TA via a cysteine residue at the N-terminus of SEQ ID NO;

45.

22. The LC of claim 21, wherein the amino acid sequence is SEQ ID NO:

45.

23. The LC of claim 21, wherein the LC has the structure:

TA-A¹-P¹-L 

 

Formula (I)

wherein;

TA is the therapeutic agent;

A¹ is a chemical group linking TA and P¹ or L;

P¹ is a bond or comprises polyglycol; and

L is the lipid.

24. The LC of claim 21, wherein a sulfur atom of the cysteine residue of the TA is connected to A¹ via a chemical bond.

25. The LC of claim 23, wherein

A¹ is selected from

26. The LC of claim 21, wherein the LC is selected from the following:

27. A pharmaceutical composition comprising the LC of claim 21.

28. A method for treating a disease or condition selected from acute heart failure, congestive heart failure, compensated heart failure, decompensated heart failure, scleroderma, diffuse scleroderma, systemic scleroderma, fibromyalgia, fibrosis, and preeclampsia;

or inducing labor in a subject in need thereof, the method comprising administering to the subject a composition comprising a therapeutically effective amount of the LC of claim 21.

29. The method of claim 28, wherein the LC is administered with one or more additional therapeutic agents selected from a group consisting of an anti-inflammatory drug, a statin, a diuretic, a beta-blocker, an angiotensin converting enzyme inhibitor, an angiotensin II receptor blocker or any combination thereof.