Immunoglobulins and uses thereof

Patent metadata

Field	Value
Publication number	US-10787495-B2
Application number	US-201916542751-A
Country	US
Kind code	B2
Filing date	Aug 16, 2019
Priority date	Oct 27, 2016
Publication date	Sep 29, 2020
Grant date	Sep 29, 2020

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. A conjugate comprising:
a. a monoclonal antibody, wherein the 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; and
b. at least one pharmacologically active moiety.

2. The conjugate of claim 1 , wherein the monoclonal antibody further comprises a Fc portion.

3. The conjugate of claim 2 , wherein the monoclonal antibody comprises 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.

4. The conjugate of claim 1 , wherein the pharmacologically active moiety is a therapeutic peptide.

5. The conjugate of claim 4 , wherein the therapeutic peptide is conjugated to the monoclonal antibody thereof at the cysteine residue of the polypeptide sequence of SEQ ID NO:18.

6. The conjugate of claim 4 , wherein the therapeutic peptide is conjugated to the monoclonal antibody via a linker.

7. The conjugate of claim 6 , 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.

8. The conjugate of claim 4 , wherein the therapeutic peptide is selected from the group consisting of oxyntomodulin, glucagon-like peptide 1 (GLP1), exendin, amylin, 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.

9. The conjugate of claim 8 , wherein the therapeutic peptide is oxyntomodulin comprising the polypeptide sequence of SEQ ID NO:24.

10. A pharmaceutical composition comprising the conjugate of claim 1 and a pharmaceutically acceptable carrier.

11. A conjugate comprising:
a. a monoclonal antibody, wherein the monoclonal antibody comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, a HCDR3, 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; and
b. two different pharmaceutically active moieties.

12. The conjugate of claim 11 , wherein the 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.

13. The conjugate of claim 11 , wherein the monoclonal antibody further comprises a Fc portion.

14. The conjugate of claim 13 , wherein the monoclonal antibody comprises 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.

15. The conjugate of claim 11 , wherein the two different pharmacologically active moieties are therapeutic peptides.

16. The conjugate of claim 15 , wherein each of the therapeutic peptides is conjugated to the monoclonal antibody at the cysteine residue of the polypeptide sequence of SEQ ID NO:18.

17. The conjugate of claim 15 , wherein each of the therapeutic peptides is conjugated to the monoclonal antibody via a linker.

18. The conjugate of claim 17 , wherein the linker independently 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.

19. The conjugate of claim 15 , wherein the therapeutic peptides are selected from the group consisting of a peptide tyrosine tyrosine (PYY) peptide, oxyntomodulin, giucagonlike peptide 1 (GLP1), exendin, amylin, 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.

20. A pharmaceutical composition comprising the conjugate of claim 11 and a pharmaceutically acceptable carrier.

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 J
• Chi Ellen

Classifications

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P3/08

  for glucose homeostasis (pancreatic hormones A61P5/48) · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title