Chimeric natriuretic peptide compositions and methods of preparation

• US 9,623,085 B2
• Filed: 11/06/2015
• Issued: 04/18/2017
• Est. Priority Date: 09/02/2011
• Status: Active Grant

• Current Assignee: Capricor Therapeutics, Inc.
• Original Assignee: Capricor Therapeutics, Inc.
• Inventors: Van Antwerp, William, Walsh, Andrew J. L., Luo, Lian, Judd, Dianne L.
• Primary Examiner(s): Shafer, Shulamith H
• Application Number:
  US14/934,617
• Publication Number:
  US 20160051632A1
• Time in Patent Office: 529 Days
• Field of Search: None
• 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 38/2242 Atrial natriuretic factor complex: Atriopeptins, atrial natriuretic protein [ANP]; Cardionatrin, Cardiodilatin
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: C07K 14/58 Atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Cardionatrin; Cardiodilatin
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

Therapeutic compositions containing chimeric natriuretic peptides for treating chronic kidney disease alone, heart failure alone, or chronic kidney disease with concomitant heart failure are described. The therapeutic compositions have enhanced stability characteristics to facilitate storage and delivery by provisioning apparatuses under conditions of elevated temperature and mechanical stress. Methods for increasing the stability of therapeutic compositions containing chimeric natriuretic peptides are further described.

Claims

1. A composition comprising:

a peptide selected from the group consisting of CD-NP (Seq. ID. No.

     1), CU-NP (Seq. ID No.

     4), B-CDNP (Seq. ID. No.

     8), and CDNP-B (Seq. ID. No.

     9), wherein the peptide is present in a concentration from about 0.05 mg/mL to about 20 mg/mL;

one or more buffers selected from the group consisting of tris(hydroxymethyl)aminomethane and a phosphate buffer, wherein the concentration of tris(hydroxymethyl)aminomethane is from about 5 to about 100 mM;

meta cresol, wherein the concentration of meta-cresol is from about 0.15 to about 0.315% by weight;

glycerol, wherein the concentration of glycerol is from about 0.1 to about 5% by weight;

and water;

wherein the composition is formed in a degassed medium; and

,

wherein the composition has a pH from about 6.5 to about 7.6 when adjusted to a temperature of 25°

C.

2. The composition of claim 1, wherein the composition comprises tris(hydroxymethyl)aminomethane at a concentration of about 50 mM, and meta-cresol at a concentration of about 0.25% by weight.

3. The composition of claim 2, wherein the concentration of said glycerol is about 1.6% by weight of the composition.

4. The composition of claim 3, wherein the composition has a pH of about 7.3.

5. The composition of claim 1, wherein the composition further comprises sodium chloride at a concentration from about 0.2 to about 10 grams per liter.

6. The composition of claim 5, wherein the composition comprises a phosphate buffer at a concentration from about 0.2 to about 10 grams per liter.

7. The composition of claim 1, wherein the composition is stored in a container where any headspace present has been purged with nitrogen or a noble gas to substantially remove oxygen from the headspace of the container.

8. The composition of claim 1, wherein the peptide is CD-NP (Seq. ID. No. 1).

9. The composition of claim 1, wherein the peptide is CU-NP (Seq. ID No. 4).

10. The composition of claim 1, wherein the peptide is B-CDNP (Seq. ID. No. 8).

11. The composition of claim 1, wherein the peptide is CDNP-B (Seq. ID. No. 9).

12. A composition comprising:

CD-NP (Seq. ID. No.

     1), wherein CD-NP is present in a concentration from about 0.05 mg/mL to about 20 mg/mL;

one or more buffers selected from the group consisting of tris(hydroxymethyl)aminomethane and a phosphate buffer, wherein the concentration of tris(hydroxymethyl)aminomethane is from about 5 to about 100 mM;

meta cresol, wherein the concentration of meta-cresol is from about 0.15 to about 0.315% by weight;

glycerol, wherein the concentration of glycerol is from about 0.1 to about 5% by weight;

and water;

wherein the composition is formed in a degassed medium; and

,

wherein the composition has a pH from about 6.5 to about 7.6 when adjusted to a temperature of 25°

C.

13. A composition comprising:

CU-NP (Seq. ID No.

     4), wherein CU-NP is present in a concentration from about 0.05 mg/mL to about 20 mg/mL;

one or more buffers selected from the group consisting of tris(hydroxymethyl)aminomethane and a phosphate buffer, wherein the concentration of tris(hydroxymethyl)aminomethane is from about 5 to about 100 mM;

meta cresol, wherein the concentration of meta-cresol is from about 0.15 to about 0.315% by weight;

glycerol, wherein the concentration of glycerol is from about 0.1 to about 5% by weight;

and water;

wherein the composition is formed in a degassed medium; and

,

wherein the composition has a pH from about 6.5 to about 7.6 when adjusted to a temperature of 25°

C.