Engineered Fc constructs

Patent metadata

Field	Value
Publication number	US-11827682-B2
Application number	US-202117527741-A
Country	US
Kind code	B2
Filing date	Nov 16, 2021
Priority date	Jan 6, 2017
Publication date	Nov 28, 2023
Grant date	Nov 28, 2023

Abstract

The present disclosure relates to engineered IgG Fc constructs and uses thereof.

First claim

The invention claimed is:

1. An Fc construct comprising:
a) a first polypeptide comprising
i). a first Fc domain monomer;
ii). a second Fc domain monomer; and
iii). a linker joining the first Fc domain monomer to the second Fc domain monomer;

b). a second polypeptide comprising
i). a third Fc domain monomer;
ii). a fourth Fc domain monomer; and
iii). a linker joining the third Fc domain monomer to the fourth Fc domain monomer;

c). a third polypeptide comprises a fifth Fc domain monomer; and
d). a fourth polypeptide comprises a sixth Fc domain monomer;
wherein the first Fc domain monomer and fifth Fc domain monomer combine to form a first Fc domain; the second Fc domain monomer and fourth Fc domain monomer combine to form a second Fc domain; and the third Fc domain monomer and sixth Fc domain monomer combine to form a third Fc domain; each of the first and second polypeptides comprises the sequence of SEQ ID NO: 78; and each of the third and fourth polypeptides comprises the sequence of SEQ ID NO: 73.

2. A pharmaceutical composition comprising the construct of claim 1 and one or more pharmaceutically acceptable carriers or excipients.

3. A method of reducing immune cell activation of the immune response in a subject, the method comprising administering to the subject an Fc construct of claim 1 .

4. The method of claim 3 , wherein the subject has an autoimmune disease.

5. A method of treating inflammation in a subject, the method comprising administering to the subject the Fc construct of claim 1 .

6. A method of promoting clearance of autoantibodies and/or suppressing antigen presentation in a subject, the method comprising administering to the subject the Fc construct of claim 1 .

7. A composition comprising a polypeptide comprising or consisting of the sequence:

(SEQ ID NO: 78)

DKTHTCPPCPAPELLGGPSVFLEPPKPKDTLMASRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPPEEQYNSTYRVVSVLTVLHQDWLNGKE

YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDKLTKNQVSLWC

LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGGGGGGGGGGGGGGG

GGDKTHTCPPCPAPELLGGPSVFLEPPKPKDTLMISRTPEVTCVVVDVS

HEDPEVKFNWYVDGVEVHNAKTKPPEEQYNSTYRVVSVLTVLHQDWLNG

KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL

TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSDLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG,

and a polypeptide comprising or consisting of the sequence:

(SEQ ID NO: 73)

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMASRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPPEEQYNSTYRVVSVLTVLHQDWLNGKE

YKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSC

AVDGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPG.

8. A method for treating an inflammatory or autoimmune disease in a subject in need thereof, comprising administering a therapeutically effective amount of the Fc construct of claim 1 .

9. The method of claim 8 , wherein the inflammatory or autoimmune disease is selected from the group consisting of: rheumatoid arthritis (RA); systemic lupus erythematosus (SLE); ANCA-associated vasculitis; antiphospholipid antibody syndrome; autoimmune hemolytic anemia; chronic inflammatory demyelinating neuropathy; graft versus host disease; dermatomyositis; Goodpasture's Syndrome; Guillain Barre syndrome; ulcerative colitis; idiopathic thrombocytopenia purpura; Myasthenia Gravis; Kawasaki Disease; inclusion body myositis; systemic sclerosis; IgA nephropathy; Graves disease; autoimmune inner ear disease (AIED); antiphospholipid syndrome (APS); pemphigus vulgaris; pemphigus follaceus; pemphigus gestationis; paraneoplastic pemphigus; syndrome; synovitis; glomerulitis; and vasculitis.

Assignees

• Momenta Pharmaceuticals Inc

Inventors

• Bosques Carlos J
• Lansing Jonathan C
• Ortiz Daniel

Classifications

• C07K2317/52

  Constant or Fc region; Isotype · CPC title

• C07K2317/60

  characterized by non-natural combinations of immunoglobulin fragments · CPC title

• C07K16/00 Primary

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• C07K14/47 Primary

  from mammals · CPC title

• A61K39/0008

  Antigens related to auto-immune diseases; Preparations to induce self-tolerance · CPC title