FUSION PROTEINS COMPRISING IGG2 HINGE DOMAINS

• US 20170008951A1
• Filed: 09/07/2016
• Published: 01/12/2017
• Est. Priority Date: 01/27/2012
• Status: Abandoned Application

• Current Assignee: Gliknik, Inc., University of Maryland Baltimore County (University of Maryland)
• Original Assignee: Gliknik, Inc.
• Inventors: BLOCK, David S., OLSEN, Henrik
• Application Number:
  US15/258,427
• Publication Number:
  US 20170008951A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/39533 against materials from animals
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07K 14/46 from vertebrates
• CPC Class Codes: C07K 14/5434 IL-12
• CPC Class Codes: C07K 14/62 Insulins
• CPC Class Codes: C07K 14/635 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: C07K 14/70503 : Immunoglobulin superfamily
• CPC Class Codes: C07K 14/70521 : CD28, CD152
• CPC Class Codes: C07K 14/70539 : MHC-molecules, e.g. HLA-molecules
• CPC Class Codes: C07K 14/7155 : for interleukins [IL]
• 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 16/2863 : against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 16/32 : against translation products of oncogenes
• CPC Class Codes: C07K 2317/41 : Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/52 : Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/53 : Hinge
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/71 : Decreased effector function due to an Fc-modification
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide
• CPC Class Codes: C07K 2319/30 : Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/31 : fusions, other than Fc, for prolonged plasma life, e.g. albumin
• CPC Class Codes: C07K 2319/55 : containing a fusion with a toxin, e.g. diphteria toxin
• CPC Class Codes: C07K 2319/60 : containing spectroscopic/fluorescent detection, e.g. green fluorescent protein [GFP]

Abstract

The present invention relates to biologically active fusion proteins containing the IgG2 hinge as a multimerization domain capable of multimerizing proteins, peptides and small molecules which are active or more active in multimeric form; compositions comprising such fusion proteins; and methods of making and using such fusion proteins.

Claims

1-151. -151. (canceled)

152. A fusion protein comprising an IgG2 hinge domain monomer and an immunoglobulin Fc domain monomer, wherein the immunoglobulin Fc domain monomer is selected for poor binding to Fc gamma receptors.

153. The fusion protein of claim 152, wherein the IgG2 hinge domain monomer is at least 95% homologous to SEQ ID NO:

1.

154. The fusion protein of claim 152, wherein the IgG2 hinge domain monomer is 100% homologous to SEQ ID NO:

1.

155. The fusion protein of claim 152, wherein the IgG2 hinge domain monomer comprises at least two C-X-X-C motifs.

156. The fusion protein of claim 155, wherein the XX in the C-X-X-C motif comprises V-E or P-P.

157. The fusion protein of claim 152, wherein the immunoglobulin Fc domain monomer is an IgG1, IgG2, IgG3 or IgG4 Fc domain monomer selected for poor binding to Fc gamma receptors.

158. The fusion protein of claim 152, wherein the immunoglobulin Fc domain monomer is an IgE Fc domain monomer.

159. The fusion protein of claim 152 or 157 wherein said immunoglobulin Fc domain monomer is mutated to bind poorly to Fc gamma receptors.

160. The fusion protein of claim 159, wherein said Fc domain is mutated at one or more of positions 233, 234, 235, 236, 238, 239, 265, 269, 270, 292, 293, 295, 296, 297, 303, 327, 329, 338, 376, and/or 414.

161. The fusion protein of claim 152 or 157 wherein said immunoglobulin Fc domain monomer is modified to bind poorly to Fc gamma receptors.

162. The fusion protein of claim 161 wherein the Fc domain is modified by hyperfucosylation, demannosylation, or hemi-glycosylation.

163. A fusion protein comprising an IgG2 hinge domain monomer and an immunoglobulin Fc domain monomer, wherein the immunoglobulin Fc domain monomer is mutated at one or more of positions 233, 234, 235, 236, 238, 239, 265, 269, 270, 292, 293, 295, 296, 297, 303, 327, 329, 338, 376, and/or 414 and wherein the Fc domain monomer binds poorly to Fc gamma receptors.

164. The fusion protein of claim 163, wherein the immunoglobulin Fc domain monomer is an IgE, IgG1, IgG2, IgG3 or IgG4 Fc domain monomer.

165. The fusion protein of claim 163 wherein the immunoglobulin Fc domain monomer is an IgG1 Fc domain monomer.