Immunoglobulins and uses thereof

Patent metadata

Field	Value
Publication number	US-10428134-B2
Application number	US-201715794250-A
Country	US
Kind code	B2
Filing date	Oct 26, 2017
Priority date	Oct 27, 2016
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

Abstract

The present invention relates to a monoclonal antibody platform designed to be coupled to therapeutic peptides to increase the half-life of the therapeutic peptide in a subject. The invention also relates to pharmaceutical compositions and methods for use thereof.

First claim

What is claimed:

1. An isolated monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, a HCDR3, and a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3, having the polypeptide sequences of SEQ ID NO: 16, 17, 18, 19, 20, and 21, respectively.

2. The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein the isolated monoclonal antibody comprises a heavy chain variable domain (VH) having the polypeptide sequence of SEQ ID NO:12, and a light chain variable domain (VL) having the polypeptide sequence of SEQ ID NO:14.

3. The isolated monoclonal antibody of claim 1 , further comprising a Fc portion.

4. The isolated monoclonal antibody of claim 3 , comprising a heavy chain (HC) having the polypeptide sequence of SEQ ID NO:13, and a light chain (LC) having the polypeptide sequence of SEQ ID NO:15.

5. An isolated nucleic acid encoding the monoclonal antibody or antigen binding fragment thereof of claim 1 .

6. A vector comprising the isolated nucleic acid of claim 5 .

7. A host cell comprising the vector of claim 6 .

8. A method of producing an isolated monoclonal antibody or antigen binding fragment thereof, the method comprising culturing the host cell of claim 7 under conditions to produce the monoclonal antibody or antigen binding fragment thereof, and recovering the antibody or antigen-binding fragment thereof from the cell or culture.

9. A conjugate comprising a monoclonal antibody or antigen-binding fragment thereof of claim 1 and at least one pharmacologically active moiety conjugated thereto.

10. A pharmaceutical composition comprising the conjugate of claim 9 and a pharmaceutically acceptable carrier.

11. A method of producing a pharmaceutical composition comprising the conjugate of claim 9 , the method comprising combining the monoclonal antibody or antigen-binding fragment thereof with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

12. The conjugate of claim 9 , wherein the pharmacologically active moiety is a therapeutic peptide.

13. The conjugate of claim 12 , wherein the therapeutic peptide is conjugated to the monoclonal antibody or antigen-binding fragment thereof at the cysteine residue of SEQ ID NO:18.

14. The conjugate of claim 12 , wherein the therapeutic peptide is conjugated to the monoclonal antibody or antigen-binding fragment thereof via a linker.

15. The conjugate of claim 14 , wherein the linker comprises a peptide linker, a hydrocarbon linker, a polyethylene glycol (PEG) linker, a polypropylene glycol (PPG) linker, a polysaccharide linker, a polyester linker, or a hybrid linker consisting of PEG and an embedded heterocycle.

16. The conjugate of claim 12 , wherein the therapeutic peptide is selected from the group consisting of oxyntomodulin, glucagon-like peptide 1 (GLP1), exendin (exenatide), amylin (pramlintide), alpha-melanocyte stimulating hormone (MSH), cocaine- and amphetamine-regulated transcript (CART), neuropeptide Y receptor Y1 (NPY1) antagonists, neuropeptide Y receptor Y5 (NPY5) antagonists, neurotensin S, neuropeptide B, neuropeptide W, ghrelin, bombesin-like receptor 3 (BRS3), galanin, cholecystokinin (CCK), orexin, melanin-concentrating hormone (MCH), oxytocin, and stresscopin.

17. The conjugate of claim 16 , wherein the therapeutic peptide is oxyntomodulin comprising the polypeptide sequence of SEQ ID NO:24.

18. A method of producing a conjugate comprising a monoclonal antibody or antigen-binding fragment thereof and a therapeutic peptide, comprising reacting an electrophile, introduced onto a sidechain of the therapeutic peptide, with the sulfhydryl group of the cysteine residue of SEQ ID NO:18 of the monoclonal antibody or antigen-binding fragment thereof as set forth in claim 1 .

19. The method of claim 18 , wherein the electrophile is bromoacetamide or maleimide.

20. A method of increasing the half-life of a therapeutic peptide in a subject, the method comprising conjugating the therapeutic peptide with a monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, a HCDR3, and a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3, having the polypeptide sequences of SEQ ID NO: 16, 17, 18, 19, 20, and 21, respectively, wherein the therapeutic peptide is conjugated to the monoclonal antibody or antigen-binding fragment thereof at the Cys residue of SEQ ID NO:18.

21. The method of claim 20 , wherein the therapeutic peptide is selected from the group consisting of oxyntomodulin, glucagon-like peptide 1 (GLP1), exendin (exenatide), amylin (pramlintide), alpha-melanocyte stimulating hormone (MSH), cocaine- and amphetamine-regulated transcript (CART), neuropeptide Y receptor Y1 (NPY1) antagonists, neuropeptide Y receptor Y5 (NPY5) antagonists, neurotensin S, neuropeptide B, neuropeptide W, ghrelin, bombesin-like receptor 3 (BRS3), galanin, cholecystokinin (CCK), orexin, melanin-concentrating hormone (MCH), oxytocin, and stresscopin.

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Macielag Mark
• Patch Raymond J
• Zhang Rui
• Case Martin A
• Rangwala Shamina M
• Leonard James N
• Camacho Raul C
• Hunter Michael J
• D'Aquino Katharine E
• Edwards Wilson
• Swanson Ronald V
• Jian Wenying
• Zhang Yue-Mei
• Wall Mark
• Chi Ellen

Classifications

• C07K14/57545 Primary

  Neuropeptide Y · CPC title

• C07K1/1072

  by covalent attachment of residues or functional groups · CPC title

• C07K1/061

  using protecting groups · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/24

  against cytokines, lymphokines or interferons · CPC title