Engineered IgA antibodies and methods of use
AssigneeTigaTX, Inc.
InventorsJeanette Henrica Wilhelmina Leusen, Johannes Gerardus Maria Evers, Geert Jan Van Tetering
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Abstract
Provided herein are engineered antibodies that comprise a modified IgA heavy chain constant region, pharmaceutical compositions, and methods of use. The engineered antibodies described herein comprise one or more amino acid substitution or deletion in a constant region of an IgA domain. Further provided herein are methods of treating disorders, including cancer, by administering an engineered IgA antibody described herein.
Claims26
A method of treating a subject in need thereof, comprising:
- administering to the subject a therapeutically effective amount of an engineered immunoglobulin A (IgA) antibody or a functional fragment thereof, wherein the engineered IgA antibody or a functional fragment thereof comprises an antibody antigen binding domain;
- and a constant domain, wherein the constant domain comprises an IgA heavy chain constant region, wherein the IgA heavy chain constant region comprises an IgA CH1 region, an IgA CH2 region, and an IgA CH3 region, wherein
- (a) the IgA CH1 region comprises an amino acid substitution of N45.2, and
- (b) the IgA CH3 region comprises a deletion of residues P131 to Y148,
- each relative to a wildtype (WT) IgA heavy chain constant region comprising the amino acid of sequence SEQ ID NO:
- 1, numbering according to IMGT scheme, wherein the therapeutically effective amount is sufficient to treat the subject.
A method of treating a subject in need thereof, comprising:
- administering to the subject a therapeutically effective amount of an engineered immunoglobulin A (IgA) antibody or a functional fragment thereof and a pharmaceutically acceptable carrier, diluent or excipient, wherein the engineered IgA antibody or a functional fragment thereof comprises an antibody antigen binding domain;
- and
- a constant domain, wherein the constant domain comprises an IgA heavy chain constant region, wherein the IgA heavy chain constant region comprises an IgA CH1 region, an IgA CH2 region, and an IgA CH3 region, wherein the IgA CH3 region comprises:
- (a) an amino acid substitution at N135, and
- (b) a deletion of C147 and Y148,
- each relative to a wildtype (WT) IgA heavy chain constant region comprising the amino acid sequence of SEQ ID NO:
- 1, numbering according to IMGT scheme, wherein the therapeutically effective amount is sufficient to treat the subject.
A method of treating a cancer in a subject in need thereof, comprising:
- administering to the subject a therapeutically effective amount of an engineered antibody or a functional fragment thereof that comprises:
- a) an antigen binding domain that binds to a cancer antigen;
- and
- b) a constant domain, wherein the constant domain comprises an immunoglobulin A (IgA) heavy chain constant region,
- wherein the IgA heavy chain constant region comprises an IgA CH1 region, IgA CH2 region, and an IgA CH3 region,
- wherein the IgA heavy chain constant region comprises:
- i) an amino acid substitution at P124, and
- ii) a deletion of residues P131 to Y148,
- each relative to a wildtype (WT) IgA heavy chain constant region comprising the amino acid sequence of SEQ ID NO:
- 1, numbering according to IMGT scheme, wherein the therapeutically effective amount is sufficient to treat the subject.
Dependencies are inferred from the claim text.