Personalized production of biologics and method for reprogramming somatic cells

• US 9,512,200 B2
• Filed: 01/03/2012
• Issued: 12/06/2016
• Est. Priority Date: 01/03/2011
• Status: Active Grant

• Current Assignee: Avm Biotechnology, Llc
• Original Assignee: Avm Biotechnology, Llc
• Inventors: Deisher, Theresa A.
• Primary Examiner(s): Landsman, Robert
• Assistant Examiner(s): Hissong, Bruce D
• Application Number:
  US13/342,704
• Publication Number:
  US 20120171722A1
• Time in Patent Office: 1,799 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: C07K 14/00 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C12N 2510/02 Cells for production
• CPC Class Codes: C12N 2517/04 Cells produced using nuclear transfer
• CPC Class Codes: C12N 5/0696 Artificially induced pluripotent stem cells, e.g. iPS

Abstract

The invention provides a method for producing polypeptide protein products and nucleic acid products having reduced levels of antigenicity in an animal being treated with a biologic product. Somatic cells are isolated from an animal, transformed into pluripotent stem cells, transfected with a nucleic acid(s) of interest, and re-differentiated towards somatic cells known to be high level producers of the desired nucleic acid product. The invention can be used to derive a general cell line to treat populations, racial specific cell lines to treat ethnic groups, or patient specific cell lines to treat individuals. Additionally, the invention provides a method to allow induced pluripotent stem cells to be re-differentiated towards their somatic cell of origin so that the cells can be used to therapeutically treat an animal without resulting teratoma formation.

Claims

1. A method for producing an isolated therapeutic recombinant biologic polypeptide or protein for treating a disease comprising transfecting a synthetically-produced Pluripotent Stem Cell (spPSC) with a nucleic acid that encodes for said therapeutic recombinant biologic polypeptide or protein, under conditions wherein the polypeptide or protein is expressed by said spPSC, and the polypeptide or protein is then isolated from the spPSC, and the spPSC is produced from a cell of an animal.

2. The method of claim 1, wherein the therapeutic recombinant biologic polypeptide or protein is selected from the group consisting of:

growth hormones, cytotoxic biologics, and monoclonal antibodies.

3. The method of claim 1 wherein the therapeutic biologic polypeptide or protein is selected from the group consisting of erythropoietin, factor VIII, factor IX, thrombin, an antibody or antibody fragment, alpha interferon, interferon alpha 2A and 2B, beta interferon, growth hormone, antihemophilic factor, G-CSF, GM-CSF, a soluble receptor, TGF-β

, bone morphogenic proteins (BMP), TGFα

, interleukin 2, β

-glucocerebrosidase or an analogue thereof, alpha1-proteinase inhibitor, fibrin, fibrinogen, von Willebrand factor, imiglucerase, agalsidase beta, laronidase, glucosidase alpha, thyrotropin alpha, and thymosin alpha.

4. The method of claim 2 wherein the antibody or antibody fragment binds to a target, wherein said target is selected from the group consisting of a tumor necrosis factor (TNF) molecule, a tumor necrosis factor receptor (TNFR), a growth factor receptor, a vascular endothelial growth factor (VEGF) molecule, interleukin 1, interleukin 4, interleukin 6, interleukin 11, interleukin 12, gamma interferon, receptor activator of nuclear factor kappa-B ligand (RANKL) and Blys.

5. The method of claim 2 wherein said soluble receptor binds to a target selected from the group consisting of TNFα

, TNFβ and

Blys.

6. The method of claim 1 further comprising immortalizing the transfected spPSC.

7. The method of claim 6 further comprising inducing differentiation of the transfected, immortalized spPSCs.

8. The method of claim 1 further comprising inducing differentiation of the transfected spPSCs.

9. The method of claim 8 further comprising immortalizing the transfected, differentiated cells.

10. The method of claim 1 wherein the spPSC is selected from the group consisting of transfected non-pluripotent cells, pluripotent stem cells produced by Somatic cell nuclear transfer (SCNT pluripotent stem cells), pluripotent stem cells produced by Altered nuclear transfer, oocyte assisted reprogramming (ANT-OAR pluripotent stem cells) and pluripotent stem cells produced by parthenogenesis (PGA pluripotent).