IL-23p40 specific immunoglobulin derived proteins, compositions, epitopes, methods and uses

• US 20060067936A1
• Filed: 09/23/2005
• Published: 03/30/2006
• Est. Priority Date: 09/24/2004
• Status: Active Grant

• Current Assignee: Centocor Incorporated (Johnson & Johnson)
• Original Assignee: Centocor Incorporated (Johnson & Johnson)
• Inventors: Luo, Jeffrey, Cunningham, Mark, Benson, Jacqueline
• Granted Patent: US 7,252,971 B2
• Time in Patent Office: Days
• US Class Current: 424/145.100
• CPC Class Codes: C07K 16/244 Interleukins [IL]
• 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: G01N 33/6869 Interleukin

Abstract

An anti-IL-23 specific human Ig derived protein, isolated nucleic acids that encode at least one anti-IL-23 Ig derived protein, vectors, host cells, transgenic animals or plants, and methods of making and using thereof are useful as therapeutic and diagnostic compositions, methods and devices. The anti-IL-23 Ig derived protein preferably binds to one or more of the Seg 1, Seg 2, and Seg 3 epitopes of the p40 subunit of IL-23.

Claims

1. An isolated anti-IL-23 Ig derived protein, comprising at least two CDRs, wherein said Ig derived protein specifically binds the p40 subunit of IL-23 and does not bind the p19 subunit of IL-23 or the p40 subunit of IL-12.

2. The isolated anti-IL-23 Ig derived protein of claim 1, wherein said Ig derived protein specifically binds the p40 subunit of human IL-23 and does not bind the p19 subunit of human IL-23 or the p40 subunit of human IL-12.

3. The isolated anti-IL-23 Ig derived protein of claim 1, wherein said Ig derived protein specifically binds at least one epitope of human IL-23p40 selected from the group consisting of amino acids 97-101 of SEQ ID NO:

1, amino acids 138-145 of SEQ ID NO;

1, and amino acids 250-269 of SEQ ID NO;

1.

5. The isolated anti-IL-23 Ig derived protein according to claim 3, wherein said Ig derived protein inhibits IL-23 activity on at least one antigen presenting cell (APC), lymphocyte, autoreactive T cell, nerve cell, and myelin cell.

6. The isolated anti-IL-23 Ig derived protein according to claim 5, wherein said APC or lymphocyte is in a tissue within the central nervous system.

7. The isolated anti-IL-23 Ig derived protein according to claim 5, wherein said APC or lymphocyte is in a tissue outside of the central nervous system.

8. The isolated anti-IL-23 Ig derived protein according to claim 5, wherein said APC is selected from at least one macrophage, microglia, Langerhans cell, Kuppfer cell, dendridic cell, B cell, alveolar macrophage, blood monocyte, stem cell precursor, and synovial A cell.

9. The anti-IL-23 Ig derived protein according to claim 3, wherein said Ig derived protein binds an IL-23 subunit with an affinity of at least one 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.

10. The anti-IL-23 Ig derived protein according to claim 3, wherein said Ig derived protein substantially neutralizes at least one activity of at least one immune related protein.

11. An isolated nucleic acid molecule encoding the isolated anti-IL-23 Ig derived protein according to claim 3.

12. An isolated nucleic acid vector comprising the isolated nucleic acid molecule according to claim 11.

13. A prokaryotic or eukaryotic host cell comprising the isolated nucleic acid molecule according to claim 11.

14. The host cell according to claim 13, wherein the host cell is at least one selected from COS-1, COS-7, EK293, BHK21, CHO, BSC-1, Hep G2, 653, SP2/0, 293, HeLa, myeloma, and lymphoma cells, and any derivative, immortalized or transformed cell thereof.

15. A method for producing at least one anti-IL-23 Ig derived protein, comprising translating the nucleic acid molecule according to claim 11 under conditions in vitro, in vivo or in situ, such that the anti-IL-23 Ig derived protein is expressed in detectable or recoverable amounts.

16. A composition comprising the anti-IL-23 Ig derived protein according to claim 3, further comprising an effective amount of at least one compound or protein selected from a detectable label or reporter, an immune therapeutic, 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 antineoplactic, an immunomodulation drug, an opthalmic, an otic or nasal drug, a topical drug, a nutritional drug or the like, a TNF antagonist, an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anesthetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, and a cytokine antagonist.

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

contacting or administering a composition comprising a modulating effective amount of the anti-IL-23 Ig derived protein according to claim 3, with, or to, said cell, tissue, organ or animal.

18. The method according to claim 17, wherein said effective amount is about 0.001-50 mg/kilogram of said cell, tissue, organ or animal.

19. The method according to claim 17, wherein said contacting or said administrating is 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, bolus, vaginal, rectal, buccal, sublingual, intranasal, and transdermal.

20. The method according to claim 17, further comprising administering, prior, concurrently or after said contacting or administering, at least one selected from an immune therapeutic, a TNF antagonist, an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anesthetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an IL-23 agent, a mineral, a nutritional, a thyroid agent, a vitamin, a calcium related hormone, an antidiarrheal, an antitussive, an antiemetic, an antiulcer, a laxative, an anticoagulant, an erythropoietin, a filgrastim, a sargramostim, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, an estrogen receptor modulator, a mydriatic, a cycloplegic, an alkylating agent, an antimetabolite, a mitotic inhibitor, a radiopharmaceutical, an antidepressant, an antimanic agent, an antipsychotic, an anxiolytic, a hypnotic, a sympathomimetic, a stimulant, donepezil, tacrine, an asthma medication, a beta agonist, an inhaled steroid, a leukotriene inhibitor, a methylxanthine, a cromolyn, an epinephrine or analog, dornase alpha, a cytokine and a cytokine antagonist.

21. The method according to claim 20, wherein said immune therapeutic is selected from at least one of beta-interferon 1a, beta-interferon 1b, glutiramer acetate, cyclophasphamide, azathioprine, glucocorticosteroids, methotrexate, paclitaxel, 2-chlorodeoxyadenosine, mitoxantrone, an IL-10, TGBbeta, CD4, CD52, antegren, CD11, CD18, TNFalpha, IL-1, IL-2, and/or CD4 antibody or antibody receptor fusion protein, interferon alpha, immunoglobulin, lismide, insulin-like growth factor-1 (IGF-1), elprodil, pirfenidone, and oral myelin.

22. The method according to claim 20, wherein said immune therapeutic is selected from at least one compound or protein that acts on one or more of:

autoimmune suppression of myelin destruction, immune regulation, activation, proliferation, migration and/or suppressor cell function of T-cells, inhibition of T cell receptor/peptide/MHC-II interaction, induction of T cell anergy, deletion of autoreactive T cells, reduction of trafficking across the blood brain barrier, alteration of balance of pro-inflammatory (Th1) or immunomodulatory (Th2) cytokines, inhibition of matrix metalloprotease inhibitors, neuroprotection, reduction of gliosis, and promotion of re-myelination.

23. The method according to claim 17, wherein said IL-23 related condition is selected from at least one of psoriasis, multiple sclerosis, optic neuritis, Crohn'"'"'s disease, psoriatic arthritis, sarcoidosis, Type I diabetes mellitus, systemic lupus erythematosus, and uveitis.

24. A medical device, comprising the anti-IL-23 Ig derived protein according to claim 3, wherein said device is suitable to contact or administer said at least one anti-IL-23 Ig derived protein 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, bolus, vaginal, rectal, buccal, sublingual, intranasal, and transdermal.

25. An article of manufacture for human pharmaceutical use, comprising packaging material and a container comprising a solution or a lyophilized form of the anti-IL-23 Ig derived protein according to claim 3.

26. The article of manufacture of claim 25, 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, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal delivery device or system.

27. A method for producing the anti-IL-23 Ig derived protein according to claim 3, comprising providing a host cell, transgenic animal, transgenic plant or plant cell capable of expressing in recoverable amounts said Ig derived protein.

28. An anti-IL-23 Ig derived protein produced by the method according to claim 27.

29. An anti-idiotype antibody or fragment specifically binding the Ig derived protein according to claim 3.

30. An Ig derived protein competitively inhibiting the binding of the Ig derived protein according to claim 3 to a ligand.

4. An isolated anti-IL-23 Ig derived protein, comprising at least two CDRs, wherein said Ig derived protein specifically binds the p40 subunit of human IL-23 at amino acids 138-145 of SEQ ID NO:

1 and said Ig derived protein does not bind the p40 subunit of human IL-12.

31. A method of screening for or selecting an anti-IL-23 Ig derived protein, comprising using a variant human p40 subunit of IL-23, wherein the variant human p40 subunit of IL-23 is replaced by all or a portion of at least one member selected from the group consisting of Murineseg 1 of murine IL-23p40, Murineseg 2 of murine IL-23p40, and Murineseg 3 of murine IL-23p40.

32. The method of claim 31, wherein the amino acid sequence of Seg 2 of human IL-23p40 is replaced by the Murineseg 2 of murine IL-23p40.

33. A method of screening for or selecting an anti-IL-23 Ig derived protein, comprising using a variant murine p40 subunit of IL-23, wherein the variant murine p40 subunit of IL-23 is replaced by all or a portion of at least one member selected from the group consisting of Seg 1 of human IL-23p40, Seg 2 of human IL-23p40, and Seg 3 of human IL-23p40.

34. The method of claim 33, wherein the amino acid sequence of the Murineseg 2 of murine IL-23p40 is replaced by Seg 2 of human IL-23p40.

35. An isolated polypeptide comprising the human IL-23 protein of SEQ ID NO:

1, wherein the amino acid sequence of Seg 2 of human IL-23p40 is replaced by the Murineseg 2 of murine IL-23p40.

36. An isolated polypeptide comprising the murine IL-23 protein, wherein the Murineseg 2 of murine IL-23p40 is replaced by the amino acid sequence of Seg 2 of human IL-23p40.

37. Any invention described herein.