Anti-IL-6 antibodies

• US 8,623,362 B2
• Filed: 06/15/2012
• Issued: 01/07/2014
• Est. Priority Date: 04/29/2005
• Status: Active Grant

• Current Assignee: Janssen Biotech, Inc. (Johnson & Johnson)
• Original Assignee: Applied Molecular Evolution, Inc. (Eli Lilly and Company), Janssen Biotech, Inc. (Johnson & Johnson)
• Inventors: Chen, Yan, Gardner, Debra, Knight, David M., Lark, Michael W., Liang, Bailin, Shealy, David J., Song, Xiao-Yu R., Stojanovic-Susulic, Vedrana, Sweet, Raymond W., Tam, Susan H., Wu, Sheng-Jiun, Yang, Jing, Marquis, David Matthew, Smith, Eric Michael, Vasserot, Alain Philippe
• Primary Examiner(s): MERTZ, PREMA MARIA
• Application Number:
  US13/524,684
• Publication Number:
  US 20130017208A1
• Time in Patent Office: 571 Days
• Field of Search: None
• US Class Current: 424/139.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 5/50 : for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07K 16/248 : IL-6
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/33 : Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• 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 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 : Framework region [FR]
• 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

Abstract

An anti-IL-6 antibody, including isolated nucleic acids that encode at least one anti-IL-6 antibody, vectors, host cells, transgenic animals or plants, and methods of making and using thereof have applications in diagnostic and/or therapeutic compositions, methods and devices.

Claims

1. A liquid pharmaceutical formulation of an isolated IL-6 antibody, comprising at least one light chain variable region and one heavy chain variable region, said light chain variable region comprising:

a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO;

132 comprising the sequence S-X₁-X₂-X₃-X₄-V-X₅-Y-M-Y, wherein X₁ is A or G, X₂ is S or R, X₃ is H, I, S, or Y, X₄ is S or Y, and X₅ is S or F;

a CDRL2 amino acid sequence of SEQ ID NO;

133 comprising the sequence D-X₆-S-X₇-L-X₈-S, wherein X₆ is F, L, M, or T, X₇ is N or E, and X₈ is A or T; and

a CDRL3 amino acid sequence of SEQ ID NO;

134 comprising the sequence X₉-X₁₀-W-S-G-Y-P-Y-T, wherein X₉ is M, C, or S, and X₁₀ is Q or C;

said heavy chain variable region comprising;

a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO;

135 comprising the sequence G-F-X₁₁-X₁₂-S-X₁₃-F-A-X₁₄-S, wherein X₁₁ is T or Q, X₁₂ is F, S, or T, X₁₃ is S or P, and X₁₄ is L or M;

a CDRH2 amino acid sequence of SEQ ID NO;

136 comprising the sequence K-X₁₅-S-X₁₆-G-G-S-X₁₇-X₁₈-Y-X₁₉-X₂₀-D-T-X₂₁-X₂₂-X₂₃, wherein X₁₅ is A or I, X₁₆ is S or P, X₁₇ is Y or W, X₁₈ is T, E, or Y, X₁₉ is Y or F, X₂₀ is P, S, D, or F, X₂₁ is V or D, X₂₂ is T or A, and X₂₃ is G or P; and

a CDRH3 amino acid sequence of SEQ ID NO;

137 comprising the sequence Q-L-W-G-X₂₄-Y-A-L-D-X₂₅, wherein X₂₄ is S, Y, T, or N, and X₂₅ is Y, T, F, or I.

2. The pharmaceutical formulation of claim 1, comprising acetate buffer, sorbitol, and polysorbate 20.

3. The pharmaceutical formulation of claim 2, wherein the pH is about 5.0.

4. The pharmaceutical formulation of claim 1, wherein the isolated IL-6 antibody comprises a light chain variable region amino acid sequence of SEQ ID NO:

97 and a heavy chain variable region amino acid sequence of SEQ ID NO;

99.

5. The pharmaceutical formulation of claim 4, comprising acetate buffer, sorbitol, and polysorbate 20.

6. The pharmaceutical formulation of claim 5, wherein the pH is about 5.0.

7. The pharmaceutical formulation of claim 1, wherein the isolated IL-6 antibody comprises a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:

3, a CDRL2 amino acid sequence of SEQ ID NO;

21, a CDRL3 amino acid sequence of SEQ ID NO;

29, a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO;

39, a CDRH2 amino acid sequence of SEQ ID NO;

59, and a CDRH3 amino acid sequence of SEQ ID NO;

89.

8. The pharmaceutical formulation of claim 7, comprising acetate buffer, sorbitol, and polysorbate 20.

9. The pharmaceutical formulation of claim 8, wherein the pH is about 5.0.

10. A liquid pharmaceutical formulation, comprising an isolated IL-6 antibody having a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:

3, a CDRL2 amino acid sequence of SEQ ID NO;

21, a CDRL3 amino acid sequence of SEQ ID NO;

29, a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO;

39, a CDRH2 amino acid sequence of SEQ ID NO;

59, and a CDRH3 amino acid sequence of SEQ ID NO;

89, acetate buffer, sorbitol, and polysorbate 20, wherein the pH is about 5.0.

11. A liquid pharmaceutical formulation, comprising an isolated IL-6 antibody having a light chain variable region amino acid sequence of SEQ ID NO:

97 and a heavy chain variable region amino acid sequence of SEQ ID NO;

99, acetate buffer, sorbitol, and polysorbate 20, wherein the pH is about 5.0.