Methods and systems for detecting peptide aggregates
OwnerPeter M. Tessierinventor
Life of this patent
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Abstract
Provided herein are conformation-specific antibodies which bind to protein aggregates, such as amyloid fibrils, including aggregates of glucagon and liraglutide. Also provided are methods of using the antibodies to detect protein aggregates in samples, and methods for identifying aggregate-binding antibodies.
Claims8
A composition comprising one or more antibodies, or antigen-binding fragments thereof, that specifically bind to one or more protein aggregates comprising fibrils relative to monomers, wherein the one or more protein aggregates include glucagon, liraglutide, or combinations thereof,
- wherein the one or more antibodies include one or more heavy chain variable regions, wherein the one or more heavy chain variable regions include a VHCDR3 including a sequence according to SEQ. ID NO.:
- 7, SEQ. ID NO.:
- 8, SEQ. ID NO.:
- 9, SEQ. ID NO.:
- 10, SEQ. ID NO.:
- 11, SEQ. ID NO.:
- 12, SEQ. ID NO.:
- 13, or SEQ. ID NO.:
- 14, or combinations thereof, wherein the one or more heavy chain variable regions include a VHCDR2 including a sequence according to SEQ. ID NO.:
- 1, SEQ. ID NO.:
- 2, SEQ. ID NO.:
- 3, SEQ. ID NO.:
- 4, SEQ. ID NO.:
- 5, or SEQ. ID NO.:
- 6, or combinations thereof, wherein the one or more heavy chain variable regions include a VHCDR1 including GFNIKDT (SEQ. ID NO.:
- 19), and
- wherein the one or more antibodies include one or more light chain variable regions, the one or more light chain variable regions include a VLCDR3 including a sequence according to SEQ. ID NO.:
- 15, SEQ. ID NO.:
- 16, SEQ. ID NO.:
- 17, or SEQ. ID NO.:
- 18, or combinations thereof, wherein the one or more light chain variable regions include a VLCDR1 including RASQDVNTAVA (SEQ. ID NO.:
- 20) and a VLCDR2 including SASFLYS (SEQ. ID NO.:
- 21).
A method of manufacturing one or more antibodies, or antigen-binding fragments thereof, that specifically binds to one or more protein aggregates comprising fibrils relative to monomers, comprising:
- producing a formulation including one or more proteins,
- contacting the formulation with one or more antibodies, or antigen-binding fragments thereof, that specifically binds to one or more protein aggregates comprising fibrils relative to monomers, and
- identifying binding of the one or more antibodies to the formulation to determine the level of aggregates in the formulation,
- wherein the one or more antibodies include one or more heavy chain variable regions, wherein the one or more heavy chain variable regions include a VHCDR3 including a sequence according to SEQ. ID NO.:
- 7, SEQ. ID NO.:
- 8, SEQ. ID NO.:
- 9, SEQ. ID NO.:
- 10, SEQ. ID NO.:
- 11, SEQ. ID NO.:
- 12, SEQ. ID NO.:
- 13, or SEQ. ID NO.:
- 14, or combinations thereof, wherein the one or more heavy chain variable regions include a VHCDR2 including a sequence according to SEQ. ID NO.:
- 1, SEQ. ID NO.:
- 2, SEQ. ID NO.:
- 3, SEQ. ID NO.:
- 4, SEQ. ID NO.:
- 5, or SEQ. ID NO.:
- 6, or combinations thereof, wherein the one or more heavy chain variable regions include a VHCDR1 including GFNIKDT (SEQ. ID NO.:
- 19),
- wherein the one or more antibodies include one or more light chain variable regions, the one or more light chain variable regions include a VLCDR3 including a sequence according to SEQ. ID NO.:
- 15, SEQ. ID NO.:
- 16, SEQ. ID NO.:
- 17, or SEQ. ID NO.:
- 18, or combinations thereof, wherein the one or more light chain variable regions include a VLCDR1 including RASQDVNTAVA (SEQ. ID NO.:
- 20) and a VLCDR2 including SASFLYS (SEQ. ID NO.:
- 21), and
- wherein the protein is glucagon, liraglutide, or combinations thereof.
Dependencies are inferred from the claim text.