COMPOSITIONS

• US 20190307891A1
• Filed: 03/27/2019
• Published: 10/10/2019
• Est. Priority Date: 09/30/2016
• Status: Active Grant

• Current Assignee: Sorriso Pharmaceuticals Incorporated
• Original Assignee: VHsquared Limited
• Inventors: CROWE, SCOTT, ROBERTS, KEVIN, CARLTON, TIM, MAGGOIRE, LUANA, CUBITT, MARION, WEST, MIKE, RAY, KEITH
• Granted Patent: US 11,684,677 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2039/542 oral/gastrointestinal
• CPC Class Codes: A61K 47/65 Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• CPC Class Codes: A61K 47/6845 the antibody targeting a cytokine, e.g. growth factors, VEGF, TNF, a lymphokine or an interferon
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: C07K 16/241 Tumor Necrosis Factors
• CPC Class Codes: C07K 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/569 Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

There is provided inter alia a composition comprising a TNF-alpha binding polypeptide and an IL-6R binding polypeptide.

Claims

1. A composition comprising:

(a) an antibody or antibody fragment that binds TNF-alpha, said antibody or said antibody fragment comprising three complementarity determining regions (CDR1-CDR3), wherein CDR1 comprises a sequence sharing 60% or greater sequence identity with SEQ ID NO;

1, CDR2 comprises a sequence sharing 50% or greater sequence identity with SEQ ID NO;

2 and CDR3 comprises a sequence sharing 60% or greater sequence identity with SEQ ID NO;

3; and

(b) an antibody or antibody fragment that binds IL-6R, said antibody or said antibody fragment comprising three complementarity determining regions (CDR1-CDR3), wherein CDR1 comprises a sequence sharing 60% or greater sequence identity with SEQ ID NO;

9, CDR2 comprises a sequence sharing 50% or greater sequence identity with SEQ ID NO;

10 and CDR3 comprises a sequence sharing 60% or greater sequence identity with SEQ ID NO;

11.

2. The composition according to claim 1, wherein said antibody or said antibody fragment of (a) binds to TNF-alpha with a Kd of 10-7 M or less, and said antibody or said antibody fragment of (b) binds to IL-6R with a Kd of 10-7 M or less.

3. The composition according to claim 1, wherein said antibody or said antibody fragment of (a) neutralizes human TNF-alpha cytotoxicity in an L929 assay with an EC50 of 1 nM or less, and said antibody or said antibody fragment of (b) neutralizes IL-6R in a standard gp130 ELISA assay with an EC50 of 1 nM or less.

4. The composition according to claim 2, wherein said antibody or said antibody fragment of (a) neutralizes human TNF-alpha cytotoxicity in an L929 assay with an EC50 of 1 nM or less, and said antibody or said antibody fragment of (b) neutralizes IL-6R in a standard gp130 ELISA assay with an EC50 of 1 nM or less.

5. The composition according to claim 1, wherein said antibody or said antibody fragment that binds TNF-alpha and said antibody or said antibody fragment that binds IL-6R are linked.

6. The composition according to claim 5, wherein said antibody or said antibody fragment that binds TNF-alpha and said antibody or antibody fragment that binds IL-6R are linked by a protease-labile peptide linker.

7. The composition according to claim 6, wherein the protease-labile peptide linker comprises a K and/or R residue.

8. The composition according to claim 1, wherein said antibody or antibody fragment of (a) and said antibody or antibody fragment of (b) retain neutralization activity when exposed to one or more proteases present in the small or large intestine.

9. The composition according to claim 1 wherein the composition is suitable for oral administration.

10. The composition according to claim 1, wherein the composition comprises an enteric coating.

11. The composition according to claim 9, wherein the composition comprises an enteric coating.

12. A pharmaceutical composition comprising the composition according to claim 1 and a pharmaceutically acceptable excipient.

13. A method of treating an autoimmune disease and/or an inflammatory disease comprising administering to a person in need thereof a therapeutically effective amount of the composition according to claim 1.

14. The method according to claim 13, wherein the autoimmune disease and/or inflammatory disease is inflammatory bowel disease and/or mucositis.

15. The method according to claim 14, wherein the inflammatory bowel disease is ulcerative colitis or Crohn'"'"'s disease.

16. The method according to claim 13, wherein the composition is administered orally.