Modifying binding molecules to minimize pre-exisiting interactions

Patent metadata

Field	Value
Publication number	US-11448651-B2
Application number	US-201916507880-A
Country	US
Kind code	B2
Filing date	Jul 10, 2019
Priority date	Jul 10, 2018
Publication date	Sep 20, 2022
Grant date	Sep 20, 2022

Abstract

The present disclosure is directed towards modifying binding molecules in order to minimize pre-existing binding interactions, including binding molecules engineered to minimize or mitigate background reactivity in a sample matrix caused by drug non-specific binding interactions.

First claim

What is claimed is:

1. A monoclonal antibody comprising:
a V H CDR1 region comprising the amino acid sequence SEQ ID NO: 9; a V H CDR2 region comprising the amino acid sequence of SEQ ID NO: 10; a V H CDR3 region comprising the amino acid sequence of SEQ ID NO: 11; a V L CDR1 region comprising the amino acid sequence of SEQ ID NO: 12; a V L CDR2 region comprising the amino acid sequence of LGS; a V L CDR3 region comprising the amino acid sequence of SEQ ID NO: 14; and
a C-terminal heavy chain sequence, wherein the C-terminal heavy chain sequence is SEQ ID NO: 8.

2. The antibody of claim 1 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 15, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 16.

3. The antibody of claim 1 , wherein said antibody mitigates high background signal during an immunogenicity analysis.

4. An assay comprising
(a) a solid support, wherein a first component is operably-linked to the solid support;
(b) at least one capture agent,
wherein a second component is operably-linked to the at least one capture agent,
wherein the capture agent comprises the antibody of claim 1 , and

(c) at least one detection agent,
wherein a detectable label is operably-linked to the detection agent, wherein the detection agent comprises the monoclonal antibody of claim 1 , and
wherein the first component and the second component selectively bind to one another.

5. The assay of claim 4 , wherein the first component comprises streptavidin and the second component comprises biotin.

6. An assay comprising
(a) a solid support, wherein a first component is operably-linked to the solid support;
(b) at least one capture agent, wherein a second component is operably-linked to the at least one capture agent and wherein the capture agent comprises the monoclonal antibody of claim 1 ; and
(c) at least one detection agent, wherein a detectable label is operably-linked to the detection agent and wherein the detection agent comprises dupilumab;
wherein the first component and the second component selectively bind to one another.

7. The assay of claim 6 , wherein the first component comprises streptavidin and the second component comprises biotin.

8. The assay of claim 6 , wherein the at least one capture agent does not bind an antibody that does not specifically bind to a sequence of a variable region of dupilumab.

9. The assay of claim 6 , wherein the at least one capture agent and the at least one detection agent binds to an antibody that specifically binds to a sequence of a variable region of dupilumab.

10. A method of determining a level of immunogenicity of a monoclonal antibody therapy in a subject, comprising
(a) contacting a biological sample from the subject with the assay of claim 4 under conditions suitable to allow binding of at least one antibody in the biological sample with the at least one capture agent and to the at least one detection agent, wherein the subject has been administered the monoclonal antibody therapy prior to the contacting step,
(b) detecting a signal from the at least one detection agent, and
(c) identifying the level of immunogenicity of the subject as high when the signal from (b) is above a threshold value or
(d) identifying the level of immunogenicity of the subject as low when the signal from (b) is below the threshold value.

11. The method of claim 10 , wherein the monoclonal antibody therapy comprises an antibody comprising a C-terminal heavy chain sequence comprising a sequence selected from the group consisting of SEQ ID NO: 7 and SEQ ID NO: 13.

12. The method of claim 10 , wherein the monoclonal antibody therapy comprises dupilumab.

13. The method of claim 10 , wherein the threshold is a predetermined value or a safety threshold.

14. The method of claim 10 , wherein the monoclonal antibody therapy is beginning and the level of immunogenicity is a baseline level.

15. The method of claim 10 , wherein the monoclonal antibody therapy is ongoing and the level of immunogenicity is a subsequent level.

16. The method of claim 10 , wherein the monoclonal antibody therapy is ending and the level of immunogenicity is a final level.

17. The method of claim 10 , wherein the subject has an inflammatory disease or disorder, an autoimmune disease or disorder, an allergic disease or disorder, an immune disease or disorder, a benign proliferative disease or disorder, atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, eosinophilic esophagitis, nasal polyps or any combination thereof.

Assignees

• Regeneron Pharma

Inventors

• Sumner Giane Oliveira
• Chen Jihua
• Partridge Michael
• Torri Albert
• Rajadhyaksha Manoj

Classifications

• C07K2317/526

  CH3 domain · CPC title

• G01N33/54393

  Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding · CPC title

• C07K16/42

  against immunoglobulins · CPC title

• G01N33/6854

  Immunoglobulins · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title