HUMAN ANTI-IL-23 ANTIBODIES, COMPOSITIONS, METHODS AND USES

• US 20070218064A1
• Filed: 12/28/2006
• Published: 09/20/2007
• Est. Priority Date: 12/29/2005
• Status: Active Grant

• Current Assignee: Janssen Biotech, Inc. (Johnson & Johnson)
• Original Assignee: Janssen Biotech, Inc. (Johnson & Johnson)
• Inventors: Sweet, Raymond, Carton, Jill, Rauchenberger, Robert, Cunningham, Mark, Benson, Jacqueline, Orlovsky, Yevgeniya
• Granted Patent: US 7,935,344 B2
• Time in Patent Office: Days
• US Class Current: 424/145.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/08 Antiseborrheics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/244 : Interleukins [IL]
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/52 : Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• 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 2319/00 : Fusion polypeptide
• CPC Class Codes: C07K 2319/30 : Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

A human anti-IL-23p19 antibody, including isolated nucleic acids that encode at least one anti-IL-23p19 antibody, vectors, host cells, and methods of making and using thereof have applications in diagnostic and/or therapeutic compositions, methods and devices.

Claims

1. An isolated IL-23p19 antibody, wherein said antibody is fully human generated from phage display and binds to human IL-23p19 or a fragment thereof.

2. The isolated antibody of claim 1, wherein said antibody binds to human IL-23p19 at one or more of amino acid residues 93-105 of SEQ ID NO:

145.

16. An antibody that competitively binds to IL-23p19 with the isolated IL-23p19 antibody according to any of claims 1-12.

17. The IL-23p19 antibody according to any of claims 1-12, wherein said antibody binds IL-23p19 with at least one affinity selected from at least 10⁻

9 M, at least 10<sup>−

10</sup> M, at least 10<sup>−

11</sup> M, and at least 10<sup>−

12</sup> M, at least 10<sup>−

13</sup> M, at least 10<sup>−

14</sup> M and at least 10<sup>−

15</sup> M, as determined by surface plasmon resonance or the Kinexa method.

18. An IL-23p19 antibody according to any of claims 1-15, wherein said antibody substantially modulates at least one activity of at least one IL-23 polypeptide.

19. An isolated nucleic acid molecule encoding at least one isolated IL-23p19 antibody according to any of claims 1-12.

20. An isolated nucleic acid vector comprising the isolated nucleic acid molecule according to claim 19.

21. A prokaryotic or eukaryotic host cell comprising the isolated nucleic acid molecule according to claim 19.

22. The host cell according to claim 21, wherein said host cell is at least one selected from COS-1, COS-7, HEK293, BHK21, CHO, BSC-1, Hep G2, 653, SP2/0, 293, HeLa, myeloma, or lymphoma cells, or any derivative, immortalized or transformed cell thereof.

23. A method for producing at least one IL-23p19 antibody, comprising translating the nucleic acid molecule according to claim 19 under conditions in vitro, in vivo or in situ, such that the IL-23p19 antibody is expressed in detectable or recoverable amounts.

29. A composition comprising the isolated IL-23p19 antibody according to claim 18 and at least one pharmaceutically acceptable carrier or diluent.

30. The composition according to claim 29, further comprising at least one compound or polypeptide selected from a detectable label or reporter, a TNF antagonist, an anti-infective drug, a cardiovascular (CV) system drug, a central nervous system (CNS) drug, an autonomic nervous system (ANS) drug, a respiratory tract drug, a gastrointestinal (GI) tract drug, a hormonal drug, a drug for fluid or electrolyte balance, a hematologic drug, an antineoplastic, an immunomodulation drug, an opthalmic, otic or nasal drug, a topical drug, a nutritional drug, a cytokine, and a cytokine antagonist.

31. An anti-idiotype antibody or fragment that specifically binds the IL-23p19 antibody according to claim 18.

32. A method for diagnosing or treating an IL-23 related condition in a cell, tissue, organ or animal, comprising

contacting or administering a composition comprising an effective amount of at least one antibody according to any of claims 1-12, with, or to, said cell, tissue, organ or animal.

33. The method according to claim 32, wherein the IL-23 related condition is selected from the group consisting of psoriasis, psoriatic arthritis, Crohn'"'"'s disease, multiple sclerosis, optic neuritis, and clinically isolated syndrome.

34. The method according to claim 32, wherein said effective amount is about 0.001-50 mg/kilogram of said cells, tissue, organ or animal.

35. The method according to claim 32, wherein said contacting or said administering is by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intraarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracerebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, intralesional, bolus, vaginal, rectal, buccal, sublingual, intranasal, and transdermal.

36. The method according to claim 32, further comprising administering, prior, concurrently or after said contacting or administering, at least one composition comprising an effective amount of at least one compound or polypeptide selected from a detectable label or reporter, an anti-infective drug, a cardiovascular (CV) system drug, a central nervous system (CNS) drug, an autonomic nervous system (ANS) drug, a respiratory tract drug, a gastrointestinal (GI) tract drug, a hormonal drug, a drug for fluid or electrolyte balance, a hematologic drug, an antineoplastic, an immunomodulation drug, an ophthalmic, otic or nasal drug, a topical drug, a nutritional drug, a cytokine, and a cytokine antagonist.

37. A medical device, comprising an IL-23p19 antibody according to any of claims 1-12, wherein said device is suitable for contacting or administering said IL-23p19 antibody by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracerebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, intralesional, bolus, vaginal, rectal, buccal, sublingual, intranasal, and transdermal.

38. An article of manufacture for human pharmaceutical or diagnostic use, comprising packaging material and a container comprising a solution or a lyophilized form of an IL-23p19 antibody according to any of claims 1-12.

39. The article of manufacture of claim 38, wherein said container is a component of a parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracerebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, intralesional, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal delivery device or system.

40. A method for producing an isolated IL-23p19 antibody according to any of claims 1-12, comprising providing a host cell or transgenic animal or transgenic plant or plant cell capable of expressing in recoverable amounts said antibody.

41. An IL-23p19 antibody produced by the method according to claim 40.

3. An isolated IL-23p19 antibody, comprising at least one light chain variable region, said light chain variable region comprising at least one member from the group consisting of:

a complementarity determining region light chain 1 (CDRL1) amino acid sequence selected from the group consisting of SEQ ID NOS;

46-51;

a CDRL2 amino acid sequence selected from the group consisting of SEQ ID NOS;

52-57; and

a CDRL3 amino acid sequence selected from the group consisting of SEQ ID NOS;

58-79.

5. An isolated IL-23p19 antibody, comprising the light chain variable region of claim 3 and a heavy chain variable region comprising at least one member from the group consisting of:

a CDRH1 amino acid sequence selected from the group consisting of SEQ ID NOS;

1-6;

a CDRH2 amino acid sequence selected from the group consisting of SEQ ID NOS;

7-39 and 146; and

a CDRH3 amino acid sequence selected from the group consisting of SEQ ID NOS;

40-45.

6. The isolated IL-23p19 antibody of claim 5, further comprising at least one human framework region adjacent to the at least one complementarity determining region.

4. An isolated IL-23p19 antibody, comprising at least one heavy chain variable region, said heavy chain variable region comprising at least one member from the group consisting of:

a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence selected from the group consisting of SEQ ID NOS;

1-6;

a CDRH2 amino acid sequence selected from the group consisting of SEQ ID NOS;

7-39 and 146; and

a CDRH3 amino acid sequence selected from the group consisting of SEQ ID NOS;

40-45.

7. An isolated IL-23p19 antibody, comprising at least one light chain variable region, said light chain variable region comprising:

a complementarity determining region light chain 1 (CDRL1) amino acid sequence selected from the group consisting of SEQ ID NOS;

46-51;

a CDRL2 amino acid sequence selected from the group consisting of SEQ ID NOS;

52-57; and

a CDRL3 amino acid sequence selected from the group consisting of SEQ ID NOS;

58-79.

9. An isolated IL-23p19 antibody, comprising the light chain variable region of claim 7 and a heavy chain variable region comprising:

a CDRH1 amino acid sequence selected from the group consisting of SEQ ID NOS;

1-6;

a CDRH2 amino acid sequence selected from the group consisting of SEQ ID NOS;

7-39 and 146; and

a CDRH3 amino acid sequence selected from the group consisting of SEQ ID NOS;

40-45.

8. An isolated IL-23p19 antibody, comprising at least one heavy chain variable region, said heavy chain variable region comprising:

a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence selected from the group consisting of SEQ ID NOS;

1-6;

a CDRH2 amino acid sequence selected from the group consisting of SEQ ID NOS;

7-39 and 146; and

a CDRH3 amino acid sequence selected from the group consisting of SEQ ID NOS;

40-45.

10. An isolated IL-23p19 antibody, comprising a light chain variable region amino acid sequence selected from the group consisting of SEQ ID NOS:

82-85, 93-98, 100, 102, 113-116, and 128-132.

12. An isolated IL-23p19 antibody, comprising the light chain variable region of claim 10 and a heavy chain variable region amino acid sequence selected from the group consisting of SEQ ID NOS:

80, 81, 86-92, 99, 101, 103-112, 117-127, and 147.

11. An isolated IL-23p19 antibody, comprising a heavy chain variable region amino acid sequence selected from the group consisting of SEQ ID NOS:

80, 81, 86-92, 99, 101, 103-112, 117-127, and 147.

13. An isolated IL-23p19 antibody, comprising a light chain variable region amino acid sequence having at least 95% identity to any of the amino acid sequences selected from the group consisting of SEQ ID NOS:

82-85, 93-98, 100, 102, 113-116, and 128-132.

15. An isolated IL-23p19 antibody, comprising the light chain variable region of claim 13 and a heavy chain variable region amino acid sequence having at least 95% identity to any of the amino acid sequences selected from the group consisting of SEQ ID NOS:

80, 81, 86-92, 99, 101, 103-112, 117-127, and 147.

14. An isolated IL-23p19 antibody, comprising a heavy chain variable region amino acid sequence having at least 95% identity to any of the amino acid sequences selected from the group consisting of SEQ ID NOS:

80, 81, 86-92, 99, 101, 103-112, 117-127, and 147.

24. An isolated nucleic acid molecule comprising at least one of:

a light chain variable region nucleotide sequence selected from the group consisting of SEQ ID NOS;

136-138 and 142-144; and

a heavy chain variable region nucleotide sequence selected from the group consisting of SEQ ID NOS;

133-135 and 139-141.

25. An isolated nucleic acid vector comprising the isolated nucleic acid molecule according to claim 24.

26. A prokaryotic or eukaryotic host cell comprising the isolated nucleic acid molecule according to claim 24.

27. The host cell according to claim 26, wherein said host cell is at least one selected from COS-1, COS-7, HEK293, BHK21, CHO, BSC-1, Hep G2, 653, SP2/0, 293, HeLa, myeloma, or lymphoma cells, or any derivative, immortalized or transformed cell thereof.

28. A method for producing at least one IL-23p19 antibody, comprising translating the nucleic acid molecule according to claim 24 under conditions in vitro, in vivo or in situ, such that the IL-23p19 antibody is expressed in detectable or recoverable amounts.

42. An isolated IL-23p19 antibody, comprising a light chain variable region amino acid sequence encoded by the nucleotide sequence selected from the group consisting of SEQ ID NOS:

136-138 and 142-144.

44. An isolated IL-23p19 antibody, comprising the light chain variable region sequence of claim 42 and a heavy chain variable region amino acid sequence encoded by the nucleotide sequence selected from the group consisting of SEQ ID NOS:

133-135 and 139-141.

48. An antibody that competitively binds to IL-23p19 with the isolated IL-23p19 antibody according to claim 44.

49. The IL-23p19 antibody according to claim 44, wherein said antibody binds IL-23p19 with at least one affinity selected from at least 10⁻

9 M, at least 10<sup>−

10</sup> M, at least 10<sup>−

11</sup> M, and at least 10<sup>−

12</sup> M, at least 10<sup>−

13</sup> M, at least 10<sup>−

14</sup> M, and at least 10<sup>−

15</sup> M, as determined by surface plasmon resonance or the Kinexa method.

50. The IL-23p19 antibody according to claim 44, wherein said antibody substantially modulates at least one activity of at least one IL-23 polypeptide.

51. An isolated nucleic acid molecule comprising the nucleotide sequence of any of claims 42-44.

52. An isolated nucleic acid vector comprising the isolated nucleic acid molecule according to claim 51.

53. A prokaryotic or eukaryotic host cell comprising the isolated nucleic acid molecule according to claim 51.

54. The host cell according to claim 53, wherein said host cell is at least one selected from COS-1, COS-7, HEK293, BHK21, CHO, BSC-1, Hep G2, 653, SP2/0, 293, HeLa, myeloma, or lymphoma cells, or any derivative, immortalized or transformed cell thereof.

55. A method for producing at least one IL-23p19 antibody, comprising translating the nucleic acid molecule according to claim 51 under conditions in vitro, in vivo or in situ, such that the IL-23p19 antibody is expressed in detectable or recoverable amounts.

56. A composition comprising the isolated IL-23p19 antibody according to claim 44 and at least one pharmaceutically acceptable carrier or diluent.

57. A composition according to claim 56, further comprising at least one compound or polypeptide selected from a detectable label or reporter, a TNF antagonist, an anti-infective drug, a cardiovascular (CV) system drug, a central nervous system (CNS) drug, an autonomic nervous system (ANS) drug, a respiratory tract drug, a gastrointestinal (GI) tract drug, a hormonal drug, a drug for fluid or electrolyte balance, a hematologic drug, an antineoplastic, an immunomodulation drug, an opthalmic, otic or nasal drug, a topical drug, a nutritional drug, a cytokine, and a cytokine antagonist.

58. An anti-idiotype antibody or fragment that specifically binds the IL-23p19 antibody according to claim 44.

59. A method for diagnosing or treating an IL-23 related condition in a cell, tissue, organ or animal, comprising

contacting or administering a composition comprising an effective amount of the antibody according to claim 44, with, or to, said cell, tissue, organ or animal.

60. The method according to claim 59, wherein the IL-23 related condition is selected from the group consisting of psoriasis, psoriatic arthritis, Crohn'"'"'s disease, multiple sclerosis, optic neuritis, and clinically isolated syndrome.

61. The method according to claim 59, wherein said effective amount is about 0.001-50 mg/kilogram of said cells, tissue, organ or animal.

62. The method according to claim 59, wherein said contacting or said administering is by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intraarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracerebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, intralesional, bolus, vaginal, rectal, buccal, sublingual, intranasal, and transdermal.

63. The method according to claim 59, further comprising administering, prior, concurrently or after said contacting or administering, at least one composition comprising an effective amount of at least one compound or polypeptide selected from a detectable label or reporter, an anti-infective drug, a cardiovascular (CV) system drug, a central nervous system (CNS) drug, an autonomic nervous system (ANS) drug, a respiratory tract drug, a gastrointestinal (GI) tract drug, a hormonal drug, a drug for fluid or electrolyte balance, a hematologic drug, an antineoplastic, an immunomodulation drug, an ophthalmic, otic or nasal drug, a topical drug, a nutritional drug, a cytokine, and a cytokine antagonist.

64. A medical device, comprising the IL-23p19 antibody according to claim 44, wherein said device is suitable for contacting or administering said IL-23p19 antibody by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracerebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, intralesional, bolus, vaginal, rectal, buccal, sublingual, intranasal, and transdermal.

65. An article of manufacture for human pharmaceutical or diagnostic use, comprising packaging material and a container comprising a solution or a lyophilized form of the IL-23p19 antibody according to claim 44.

66. The article of manufacture of claim 65, wherein said container is a component of a parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracerebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, intralesional, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal delivery device or system.

67. A method for producing the isolated IL-23p19 antibody according to claim 44, comprising providing a host cell or transgenic animal or transgenic plant or plant cell capable of expressing in recoverable amounts said antibody.

68. An IL-23p19 antibody produced by the method according to claim 67.

43. An isolated IL-23p19 antibody, comprising a heavy chain variable region amino acid sequence encoded by the nucleotide sequence selected from the group consisting of SEQ ID NOS:

133-135 and 139-141.

45. An isolated IL-23p19 antibody, comprising a light chain variable region sequence encoded by a nucleotide sequence having at least 95% identity to any of the nucleotide sequences selected from the group consisting of SEQ ID NOS:

136-138 and 142-144.

47. An isolated IL-23p19 antibody, comprising the light chain variable region sequence of claim 45 and a heavy chain variable region sequence encoded by a nucleotide sequence having at least 95% identity to any of the nucleotide sequences selected from the group consisting of SEQ ID NOS:

133-135 and 139-141.

46. An isolated IL-23p19 antibody, comprising a heavy chain variable region sequence encoded by a nucleotide sequence having at least 95% identity to any of the nucleotide sequences selected from the group consisting of SEQ ID NOS:

133-135 and 139-141.

69. Any invention described herein.