Injectable Polymeric Biopharmaceutical Formulations

Patent metadata

Field	Value
Publication number	US-2024252596-A1
Application number	US-202418405958-A
Country	US
Kind code	A1
Filing date	Jan 5, 2024
Priority date	Jan 5, 2023
Publication date	Aug 1, 2024
Grant date	—

Abstract

The present disclosure provides injectable pharmaceutical compositions including suspended particles in a liquid carrier, where the particles of the composition include a biopharmaceutical agent and a polyacrylamide-based copolymer. The inventors have demonstrated that particular polyacrylamide-based copolymers can be used as stabilizing excipients in particle formulations of biopharmaceutical agents, without interacting directly with the biopharmaceutical agent, or altering its pharmacokinetic properties. The pharmaceutical composition can be formulated for injection to a patient. Also provided is a syringe loaded with the injectable pharmaceutical composition, methods of administering via injection a therapeutically effective dose of a biopharmaceutical to a subject in need thereof, and methods of preparing a subject injectable pharmaceutical composition.

First claim

1 . An injectable pharmaceutical composition comprising:
particles, the particles comprising:
a biopharmaceutical agent; and
a polyacrylamide-based copolymer; and
a liquid carrier in which the particles are suspended.

2 . The injectable pharmaceutical composition of claim 1 , wherein the particles have a mean diameter of 100 microns or less.

3 - 6 . (canceled)

7 . The injectable pharmaceutical composition of claim 1 , further comprising one or more of stabilizing agent, preservative, filler, bulking agent, sugar, polysaccharide, or viscosity modifier.

8 - 9 . (canceled)

10 . The injectable pharmaceutical composition of claim 1 , wherein the biopharmaceutical agent is a polypeptide susceptible to aggregation in an aqueous medium.

11 . (canceled)

12 . The injectable pharmaceutical composition of claim 10 , wherein the polypeptide is selected from antibodies and fragments thereof, cytokines, chemokines, hormones, vaccine antigens, cancer antigens, adjuvants, and combinations thereof.

13 . The injectable pharmaceutical composition of claim 1 , wherein the biopharmaceutical agent polypeptide is a protein.

14 . The injectable pharmaceutical composition of claim 13 , wherein the protein is an antibody or a fragment thereof.

15 . The injectable pharmaceutical composition of claim 14 , wherein the protein is a monoclonal antibody, a polyclonal antibody, an immunoglobulin G (IgG) antibody, an IgA antibody, an IgM antibody, a Fc fusion protein, or a fragment thereof.

16 . The injectable pharmaceutical composition of claim 1 , wherein;
the biopharmaceutical agent is a hormone or analog thereof; the biopharmaceutical agent is insulin or an analog thereof; or the biopharmaceutical agent is selected from glucagon, GLP-1 receptor agonist, amylin, and analogs thereof.

17 - 18 . (canceled)

19 . The injectable pharmaceutical composition of claim 1 , wherein the composition comprises 0.1 to 20% by weight of the biopharmaceutical agent, wherein:
the biopharmaceutical agent is a peptide; or the biopharmaceutical agent is insulin or an analog thereof.

20 - 23 . (canceled)

24 . The injectable pharmaceutical composition of claim 1 , wherein the composition comprises 20% to 80% by weight of the biopharmaceutical agent and/or the particles comprise 75% or more by weight of the biopharmaceutical agent, wherein the biopharmaceutical agent is an antibody or fragment thereof, or a Fc fusion protein.

25 - 26 . (canceled)

27 . The injectable pharmaceutical composition of claim 1 , wherein the composition comprises 0.01 to 20 wt % of the polyacrylamide-based copolymer and/or the particles comprise 0.01 to 25 wt % of the polyacrylamide-based copolymer.

28 - 32 . (canceled)

33 . The injectable pharmaceutical composition of claim 1 , wherein weight to weight ratio of the polyacrylamide-based copolymer to the biopharmaceutical agent is 1:500 to 2:1, 1:50 to 1:1, or 1:25 to 1:10.

34 - 35 . (canceled)

36 . The injectable pharmaceutical composition of claim 1 , wherein the polyacrylamide-based copolymer comprises:
a water-soluble carrier monomer selected from N-(3-methoxypropyl)acrylamide (MPAM), 4-acryloylmorpholine (MORPH), N,N-dimethylacrylamide (DMA), N-hydroxyethyl acrylamide (HEAM), acrylamide (AM), and combinations thereof; and a functional dopant monomer selected from N-[tris(hydroxymethyl)-methyl]acrylamide (TRI), 2-acrylamido-2-methylpropane sulfonic acid (AMP), (3-acrylamidopropyl)trimethylammonium chloride (TMA), N-isopropylacrylamide (NIP), N—N-diethylacrylamide (DEA), N-tert-butylacrylamide (TBA), N-phenylacrylamide (PHE), and combinations thereof.

37 . The injectable pharmaceutical composition of claim 36 , wherein the water-soluble carrier monomer is selected from MORPH, MPAM, and combinations thereof.

38 . The injectable pharmaceutical composition of claim 37 , wherein the water-soluble carrier monomer comprises MORPH.

39 . The injectable pharmaceutical composition of claim 37 , wherein the water-soluble carrier monomer comprises MPAM.

40 . The injectable pharmaceutical composition of claim 36 , wherein the functional dopant monomer is selected from AMP, TMA, TBA, PHE, and combinations thereof.

41 . The injectable pharmaceutical composition of claim 36 , wherein the functional dopant monomer is selected from DEA, PHE, NIP, and combinations thereof.

42 . The injectable pharmaceutical composition of claim 36 , wherein the functional dopant monomer comprises TRI.

43 . The injectable pharmaceutical composition of claim 36 , wherein the functional dopant monomer comprises PHE.

44 . The injectable pharmaceutical composition of claim 36 , wherein the functional dopant monomer comprises NIP.

45 . The injectable pharmaceutical composition of claim 36 , wherein the functional dopant monomer comprises DEA.

46 . The injectable pharmaceutical composition of claim 36 , wherein:
the water-soluble carrier monomer is selected from MPAM, MORPH, and combinations thereof; and the functional dopant monomer is selected from NIP, PHE, and combinations thereof.

47 . The injectable pharmaceutical composition of claim 36 , wherein:
the water-soluble carrier monomer is selected from MPAM, MORPH, and combinations thereof; and the functional dopant monomer is selected from AMP, TMA, TBA, PHE, and combinations thereof.

48 . The injectable pharmaceutical composition of claim 36 , wherein the water-soluble carrier monomer is MPAM, and the functional dopant monomer is PHE.

49 . The injectable pharmaceutical composition of claim 36 , wherein the water-soluble carrier monomer is MORPH, and the functional dopant monomer is PHE.

50 . The injectable pharmaceutical composition of claim 36 , wherein the water-soluble carrier monomer is MORPH, and the functional dopant monomer is NIP.

51 . The injectable pharmaceutical composition of claim 36 , wherein the polyacrylamide-based copolymer comprises:
a) 70 wt % to 98 wt % of the water-soluble carrier monomer; and
2 wt % to 30 wt % of the functional dopant monomer;
b) 80 wt % to 95 wt % of the water-soluble carrier monomer; and
5 wt % to 20 wt % of the functional dopant monomer; or
c) 83 wt % to 98 wt % of the water-soluble carrier monomer; and
2 wt % to 17 wt % of the functional dopant monomer.

52 - 53 . (canceled)

54 . The injectable pharmaceutical composition of claim 36 , wherein the polyacrylamide-based copolymer comprises:
a) 70 wt % to 85 wt % of MORPH; and
15 wt % to 30 wt % of NIP;
b) 74 wt % to 80 wt % of MORPH; and
20 wt % to 26 wt % of NIP; or
c) 77 wt % of MORPH; and
23 wt % of NIP.

55 - 56 . (canceled)

57 . The injectable pharmaceutical composition of claim 36 , wherein the degree of polymerization of the polyacrylamide-based copolymer is 10 to 500, and/or the number-average molecular weight of the polyacrylamide-based copolymer is 1,000 g/mol to 40,000 g/mol.

58 - 63 . (canceled)

64 . The injectable pharmaceutical composition of claim 1 , wherein the liquid carrier comprises a mixture of an organic solvent and an aqueous solution, or wherein the l

Assignees

• Univ Leland Stanford Junior

Inventors

• Appel Eric A
• Jons Carolyn
• Prossnitz Alex

Classifications

• C07K16/06

  from serum · CPC title

• A61K9/10

  Dispersions; Emulsions · CPC title

• A61K47/14

  Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K38/22

  Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35) · CPC title