# US 11,304,994 B2 · Recombinant intravenous immunoglobulin (rIVIG) compositions and methods for their production and use > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,304,994 B2 - Document ID: US11304994B2 - Status: Granted - Kind: B2 - Application number: 16/089,042 - Filed: 2017-03-29 - Published: 2019-04-18 - Granted: 2022-04-19 - Earliest claimed: 2016-03-30 - Assignees: AB Biosciences, Inc. - Applicants: AB Biosciences, Inc. - Inventors: Yen-Ming Hsu; Jeng-Shin Lee; Hsiu-Ching Chang - Web page: https://patentgrep.com/patent/US11304994B2 ## CPC - A61K 38/47: acting on glycosyl compounds (3.2), e.g. cellulases, lactases - 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)} - A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - C07K 14/47: from mammals - C07K 14/70535: {Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)} - C07K 14/70575: {NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 (NGF C07K14/48, TNF C07K14/525)} - C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)} - C07K 14/78: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] - C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies - C12N 15/62: DNA sequences coding for fusion proteins - A61K 2039/505: {comprising antibodies} - C07K 2317/52: Constant or Fc region; Isotype - C07K 2317/522: CH1 domain - C07K 2317/53: Hinge - C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto - C07K 2319/70: containing domain for protein-protein interaction - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract Compositions of recombinant intravenous immunoglobulin (rIVIG) proteins and methods for purification and use of rIVIG proteins. The compositions comprise oligomeric Fc molecules which bind to Fc receptors with high avidity. The rIVIG proteins are useful as immunomodulatory molecules for the treatment of immune disorders including autoimmune diseases, such as refractory immune thrombocytopenia, chronic inflammatory demyelinating polyneuropathy, multiple sclerosis, lupus, Graves Disease, Kawasaki disease, dermatomyositis, myasthenia gravis, Guillain-Barre syndrome, autoimmune hemolytic anemia, and other immune and inflammatory conditions. The rIVIG proteins can also be used as immunomodulators in patients to reduce the immune rejection of organ transplants, stem cell transplants and bone marrow transplantation. Additionally, the present invention provides rIVIG proteins of non-human origin, for use in veterinary immune disorders, such as canine rIVIG proteins for the treatment of dogs suffering from autoimmune hemolytic anemia, immune thrombocytopenia purpura, rheumatoid arthritis, or other canine immune disorder. ## Claims ### Claim 1 A recombinant intravenous immunoglobulin (rIVIG) polypeptide comprising (a) a CL domain, a CH1 domain, and a single chain Fc peptide comprising two CH2-CH3 Fc domains; and (b) an oligomerization peptide domain, wherein the oligomerization peptide domain includes a collagen trimerization domain and the C-terminal end of the CL domain is linked to the N-terminal end of the CH1 domain by a short linker sequence. ### Claim 2 (depends on 1) The rIVIG polypeptide of claim 1, wherein the two CH2-CH3 Fc domains are joined via a flexible linker. ### Claim 3 (depends on 2) The rIVIG polypeptide of claim 2, wherein the flexible linker comprises from two to six repeats of the amino acid sequence G-G-G-G-S (SEQ ID NO: 9). ### Claim 4 (depends on 2) The rIVIG polypeptide of claim 2, wherein the flexible linker comprises five repeats of the amino acid sequence G-G-G-G-S (SEQ ID NO: 9). ### Claim 5 (depends on 4) The rIVIG polypeptide of claim 4, wherein the C-terminus of the oligomerization peptide domain is linked to the N-terminus of the CL domain. ### Claim 6 (depends on 5) The rIVIG polypeptide of claim 5, wherein the oligomerization peptide domain comprises amino acid nos. 1 to 79 of SEQ ID NO: 6. ### Claim 7 (depends on 4) The rIVIG polypeptide of claim 4, wherein the N-terminus of the oligomerization peptide domain is linked to the C-terminus of the single chain Fc peptide. ### Claim 8 (depends on 7) The rIVIG polypeptide of claim 7, wherein the oligomerization peptide domain comprises amino acid nos. 712 to 768 of SEQ ID NO: 4. ### Claim 9 (depends on 1) A composition for treatment of immune disorders comprising the rIVIG polypeptide of claim 1. ### Claim 10 (depends on 9) The composition of claim 9, wherein the rIVIG polypeptide comprises Fc regions of an isotype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4. ### Claim 11 (depends on 9) The composition of claim 9, wherein the rIVIG polypeptide is predominantly afucosylated. ### Claim 12 (depends on 1) A method of treating a patient suffering from an autoimmune disorder, said method comprising administering to said patient an effective amount of a composition comprising the rIVIG polypeptide of claim 1. ### Claim 13 A method of reducing the immune rejection response of a patient who has received an organ transplant, said method comprising administering to said patient an effective amount of a composition comprising recombinant immunoglobulin (rIVIG) protein, wherein said rIVIG protein comprises a CL domain, a CH1 domain, a single chain Fc peptide comprising two CH2-CH3 Fc domains, and an oligomerization peptide domain, wherein the oligomerization peptide domain includes a collagen trimerization domain and the C-terminal end of the CL domain is linked to the N-terminal end of the CH1 domain by a short linker sequence. ### Claim 14 (depends on 12) The method of claim 12, wherein the rIVIG protein comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 4 and SEQ ID NO: 6. ### Claim 15 (depends on 1) A method of treating a non-human mammal suffering from an autoimmune disorder, said method comprising administering to said non-human mammal an effective amount of a composition comprising the recombinant intravenous immunoglobulin (rIVIG) protein of claim 1, wherein said rIVIG protein comprises an amino acid sequence that has been derived from a non-human mammal of the same species. ### Claim 16 (depends on 13) The method of claim 13, wherein the rIVIG protein comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 4 and SEQ ID NO: 6. ### Claim 17 A recombinant intravenous immunoglobulin (rIVIG) polypeptide comprising (a) a CL domain, a CH1 domain, and a single chain Fc peptide comprising two CH2-CH3 Fc domains; and (b) a collagen derived peptide domain, wherein the collagen-derived peptide domain is a collagen trimerization domain and the C-terminal end of the CL domain is linked to the N-terminal end of the CH1 domain by a short linker sequence. ### Claim 18 (depends on 17) The rIVIG polypeptide of claim 17, wherein the collagen derived peptide domain comprises amino acid nos. 712 to 768 of SEQ ID NO: 4. ### Claim 19 A recombinant intravenous immunoglobulin (rIVIG) polypeptide comprising (a) a single chain Fc peptide comprising two CH2-CH3 Fc domains; and (b) a mannose binding protein (MBP) derived peptide domain, wherein the MBP-derived peptide domain includes a collagen trimerization domain. ### Claim 20 (depends on 19) The rIVIG polypeptide of claim 19, wherein the MBP-derived peptide domain comprises amino acid nos. 1 to 79 of SEQ ID NO: 6.