# US 12,005,119 B2 · Antibody biopharmaceutical formulations including polymer excipients > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,005,119 B2 - Document ID: US12005119B2 - Status: Granted - Kind: B2 - Application number: 18/200,958 - Filed: 2023-05-23 - Published: 2023-11-23 - Granted: 2024-06-11 - Earliest claimed: 2022-05-23 - Assignees: The Board of Trustees of the Leland Stanford Junior University - Applicants: The Board of Trustees of the Leland Stanford Junior University - Inventors: Eric A. Appel; Joseph L. Mann; John Klich; Catherine M. Kasse - Web page: https://patentgrep.com/patent/US12005119B2 ## CPC - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - C07K 16/1063 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract Polyacrylamide-based copolymers act as stabilizing excipients in formulations of antibody biopharmaceutical agents without interacting directly with the antibody or altering its pharmacokinetic properties. The polyacrylamide-based copolymers confer a substantial stability benefit to high concentration compositions of a variety of antibodies by precluding adsorption of the antibody to the interfaces of the composition, preventing undesirable aggregation events and maintaining the binding activity of the antibody. Such antibody compositions are useful in methods of administering the composition to a subject. ## Claims ### Claim 1 A composition comprising: a polyacrylamide-based copolymer comprising: 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; and an antibody. ### Claim 2 (depends on 1) The composition of claim 1, wherein the water-soluble carrier monomer is selected from MORPH, MPAM, and combinations thereof. ### Claim 3 (depends on 1) The composition of claim 1, wherein the functional dopant monomer is selected from AMP, TMA, TBA, PHE, and combinations thereof. ### Claim 4 (depends on 1) The composition of claim 1, wherein the functional dopant monomer is selected from DEA, PHE, NIP, and combinations thereof. ### Claim 5 (depends on 1) The composition of claim 1, wherein the functional dopant monomer comprises TRI. ### Claim 6 (depends on 1) The composition of claim 1, wherein the functional dopant monomer comprises PHE. ### Claim 7 (depends on 1) The composition of claim 1, wherein the functional dopant monomer comprises NIP. ### Claim 8 (depends on 1) The composition of claim 1, wherein the functional dopant monomer comprises DEA. ### Claim 9 (depends on 1) The composition of claim 1, 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. ### Claim 10 (depends on 1) The composition of claim 1, 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. ### Claim 11 (depends on 1) The composition of claim 1, wherein the water-soluble carrier monomer is MPAM, and the functional dopant monomer is PHE. ### Claim 12 (depends on 1) The composition of claim 1, wherein the water-soluble carrier monomer is MORPH, and the functional dopant monomer is PHE. ### Claim 13 (depends on 1) The composition of claim 1, wherein the water-soluble carrier monomer is MORPH, and the functional dopant monomer is NIP. ### Claim 14 (depends on 1) The composition of claim 1, wherein the copolymer comprises: 70 wt % to 98 wt % of the water-soluble carrier monomer; and 2 wt % to 30 wt % of the functional dopant monomer. ### Claim 15 (depends on 1) The composition of claim 1, wherein the copolymer comprises: 70 wt % to 85 wt % of MORPH; and 15 wt % to 30 wt % of NIP. ### Claim 16 (depends on 1) The composition of claim 1, comprising 0.1 wt % to 10 wt % of the copolymer, wherein a degree of polymerization of the copolymer is 10 to 500, and wherein a number-average molecular weight of the copolymer is 2,000 g/mol to 10,000 g/mol. ### Claim 17 (depends on 1) The composition of claim 1, comprising 5 wt % or more of the antibody. ### Claim 18 (depends on 17) The composition of claim 17, comprising 10 wt % or more of the antibody. ### Claim 19 (depends on 1) The composition of claim 1, comprising 2.5 wt % to 20 wt % of the antibody. ### Claim 20 (depends on 1) The composition of claim 1, wherein the antibody has a molecular weight of 100 kDa to 200 kDa. ### Claim 21 (depends on 1) The composition of claim 1, wherein the antibody is a monoclonal antibody. ### Claim 22 (depends on 1) The composition of claim 1, wherein the antibody is selected from a chimeric antibody, bispecific antibody, full-length antibody, antibody fragment, and an antibody-drug conjugate. ### Claim 23 (depends on 1) The composition of claim 1, comprising: 0.1 wt % to 10 wt % of a polyacrylamide-based copolymer comprising: 70 wt % to 98 wt % of a water-soluble carrier monomer selected from MPAM, MORPH, DMA, HEAM, AM, and combinations thereof; and 2 wt % to 30 wt % of a functional dopant monomer selected from TRI, AMP, TMA, NIP, TBA, PHE, and combinations thereof; and 5 wt % or more of the antibody. ### Claim 24 (depends on 23) The composition of claim 23, comprising 10 wt % or more of the antibody. ### Claim 25 (depends on 23) The composition of claim 23, 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. ### Claim 26 (depends on 25) The composition of claim 25, wherein: the water-soluble carrier monomer is MORPH; and the functional dopant monomer is NIP. ### Claim 27 (depends on 23) The composition of claim 23, further comprising: 0.001 wt % to 0.5 wt % of a surfactant; 0.1 wt % to 25 wt % of a stabilizer; and a buffer, wherein the composition is aqueous and has a pH of 3 to 7.5. ### Claim 28 (depends on 1) The composition of claim 1, wherein the composition is formulated for subcutaneous administration. ### Claim 29 (depends on 1) A method of administering an antibody to a subject in need thereof, comprising injecting the subject with a therapeutically effective amount of a composition according to claim 1. ### Claim 30 (depends on 1) The composition of claim 1, wherein the composition comprises a suspension of particles in a liquid carrier, wherein the particles comprise the polyacrylamide-based copolymer and the antibody.