Immunoglobulins and uses thereof

Patent metadata

Field	Value
Publication number	US-10858413-B2
Application number	US-201716344263-A
Country	US
Kind code	B2
Filing date	Oct 26, 2017
Priority date	Oct 27, 2016
Publication date	Dec 8, 2020
Grant date	Dec 8, 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

The invention claimed is:

1. A pharmaceutical composition comprising:
a. a conjugate; and
b. a pharmaceutically acceptable carrier;

wherein the conjugate comprises:
i. 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 NOs: 16, 17, 18, 19, 20, and 21, respectively; and
ii. at least one pharmacologically active moiety;

wherein the pharmaceutical composition is a solid pharmaceutical composition.

2. The pharmaceutical composition of claim 1 , 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.

3. The pharmaceutical composition of claim 2 , wherein the monoclonal antibody further comprises a Fc portion.

4. The pharmaceutical composition of claim 3 , wherein the monoclonal antibody comprises a heavy chain having the polypeptide sequence of SEQ ID NO:13, and a light chain (LC) having the polypeptide sequence of SEQ ID NO:15.

5. The pharmaceutical composition of claim 1 , wherein the pharmacologically active moiety is a therapeutic peptide.

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

7. The pharmaceutical composition of claim 5 , wherein the therapeutic peptide is conjugated to the monoclonal antibody via a linker.

8. The pharmaceutical composition of claim 7 , 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.

9. The pharmaceutical composition of claim 5 , 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.

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

11. A method of reducing food intake or treating disease or disorder in a subject in need thereof, wherein the disease or disorder is selected from the group consisting of obesity, type II diabetes, metabolic syndrome, insulin resistance, impaired glucose tolerance, hyperglycemia, hyperinsulinemia, hypertriglyceridemia, dyslipidemia, atherosclerosis, diabetic nephropathy, hypertension, non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH), the method comprising administering to the subject an effective amount of the pharmaceutical composition of claim 9 .

12. The method of claim 11 , wherein the pharmaceutical composition is administered in combination with at least one additional agent.

13. The method of claim 12 , wherein the additional agent is a glucagon-like-peptide-1 receptor modulator.

14. The method of claim 11 , wherein the pharmaceutical composition is administered in combination with liraglutide or dulaglutide.

15. The pharmaceutical composition of claim 1 , wherein the solid pharmaceutical composition is a freeze-dried or spray-dried composition.

16. The pharmaceutical composition of claim 15 , wherein the solid pharmaceutical composition is selected from a tablet, a sachet, a dragee, a powder, a granule, a lozenge, or a powder for reconstitution.

17. The pharmaceutical composition of claim 16 , wherein the table is a compressed tablet, a coated tablet, or a capsule.

Assignees

• Janssen Pharmaceutica Nv

Inventors

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