Fusion protein for treating rejection reaction in transplantation

• US 10,293,018 B2
• Filed: 09/01/2016
• Issued: 05/21/2019
• Est. Priority Date: 09/01/2015
• Status: Active Grant

• Current Assignee: Immunwork Inc.
• Original Assignee: Immunwork Inc.
• Inventors: Chang, Tse-Wen, Chu, Hsing-Mao, Du, Li-Yun
• Primary Examiner(s): Huynh, Phuong
• Application Number:
  US15/253,907
• Publication Number:
  US 20170056521A1
• Time in Patent Office: 992 Days
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 39/44 Antibodies bound to carriers
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61K 47/65 Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• CPC Class Codes: A61K 47/68 the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• CPC Class Codes: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: A61K 47/6843 the antibody targeting a material from animals or humans
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 14/70532 B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 16/36 against blood coagulation factors
• CPC Class Codes: C07K 2317/20 characterized by taxonomic origin
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide
• CPC Class Codes: C07K 2319/035 : containing a signal for targeting to the external surface of a cell, e.g. to the outer membrane of Gram negative bacteria, GPI- anchored eukaryote proteins
• 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 7/08 : having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: C12N 15/1037 : Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display
• CPC Class Codes: C12N 9/6459 : t-plasminogen activator (3.4.21.68), i.e. tPA
• CPC Class Codes: C12Y 304/21068 : Tissue plasminogen activator (3.4.21.68), i.e. tPA

Abstract

The present disclosure provides various molecular constructs having a targeting element and an effector element. Methods for treating various diseases using such molecular constructs are also disclosed.

Claims

1. A molecular construct comprising,

a pair of CH2-CH3 segments of an IgG.Fc;

a pair of effector elements, wherein each effector element is an extracellular domain of cytotoxic T lymphocyte associated protein 4 (CTLA-4) or an extracellular domain of programmed death-ligand 1 (PD-L1); and

a pair of targeting elements, wherein each targeting element is an antibody fragment specific for a human leukocyte antigen (HLA) allotype present only on cells of a donor transplant and not on cells of the recipient and comprises the amino acid sequence of SEQ ID NO;

32 or SEQ ID NO;

34, wherein,

the pair of effector elements is linked to the N-termini of the pair of CH2-CH3 segments, and the pair of targeting elements is linked to the C-termini of the pair of CH2-CH3 segments, or vice versa.

2. The molecular construct of claim 1, wherein the pair of CH2-CH3 segments is derived from human γ

1 or γ

4 immunoglobulin.

3. The molecular construct of claim 1, wherein the pair of targeting elements is in the form of an antigen-binding fragment (Fab) and is linked to the N-termini of the pair of CH2-CH3 segments, so that the molecular construct adopts an IgG configuration.

4. The molecular construct of claim 1, wherein the molecular construct comprises the amino acid sequence of SEQ ID NO:

35 or SEQ ID NO;

36.