Antibodies against human IL-12

• US 7,026,456 B1
• Filed: 08/30/2000
• Issued: 04/11/2006
• Est. Priority Date: 01/23/1998
• Status: Expired due to Term

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Gately, Maurice Kent, Presky, David Howard
• Primary Examiner(s): Gambel, Phillip
• Assistant Examiner(s): OUSPENSKI, ILIA I
• Application Number:
  US09/652,282
• Time in Patent Office: 2,050 Days
• Field of Search: 530/387.1, 530/388.23, 530/387.3, 435/346, 435/70.21, 435/332, 435/335, 435/343.1, 435/343.2, 514/2
• US Class Current: 530/388.23
• 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 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: C07K 16/244 Interleukins [IL]
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• 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
• CPC Class Codes: G01N 33/6869 Interleukin

Abstract

The present invention relates to novel p75 heterodimer specific anti-human IL-12 antibodies that are characterized by a higher potency and greater efficacy in neutralizing human IL-12 bioactivity than known heterodimer specific IL-12 monoclonal antibodies. The heterodimer specific antibodies recognize one or more epitopes of the human IL-12 p75 heterodimer, but do not bind to the p40 subunit alone. The heterodimer specific IL-12 antibodies neutralize rhesus monkey IL-12 bioactivity with a potency similar to their potency for neutralizing human IL-12 bioactivity making them useful IL-12 antagonists for in vivo studies in the rhesus monkey.

Claims

1. A monoclonal antibody to human IL-12 which consists of a p35 subunit and a p40 subunit forming a p75 heterodimer, wherein said monoclonal antibody

(a) immunologically reacts with an epitope presented by the p75 heterodimer of human IL-12, but is not immunologically reactive with any epitope presented by said p40 subunit;

and

(b) neutralizes at least about 90% of the bioactivity of human IL-12, wherein the antibody neutralizes at least about 90% bioactivity of human IL-12 by inhibiting IL-12 stimulated PHA-activated human lymphoblast proliferation wherein the concentration of said antibody is 0.5μ

g/ml and the concentration of said human IL-12 is 0.25 ng/ml.

3. The antibody of claim 1, wherein the antibody cross reacts with rhesus monkey IL-12.

4. The antibody of claim 1, wherein the antibody is humanized.

5. The antibody of claim 1, wherein the antibody is produced by a hybridoma.

6. The antibody of claim 5, wherein the antibody has been humanized.

2. A monoclonal antibody to human IL-12 which consists of a p35 subunit and a p40 subunit forming a p75 heterodimer, wherein said monoclonal antibody

(a) immunologically reacts with an epitope presented by the p75 heterodimer of human IL-12, but is not immunologically reactive with any epitope presented by said p40 subunit;

and

(b) neutralizes at least about 90% of the bioactivity of human IL-12, wherein the antibody neutralizes at least about 90% bioactivity of human IL-12 by inhibiting IL-12 stimulated IFN-γ

production by PHA-activated human lymphoblasts, wherein the concentration of the antibody is 0.5 μ

g/ml and the concentration of said human IL-12 is 0.25 ng/ml.

7. The antibody of claim 2, wherein the antibody cross reacts with rhesus monkey IL-12.

8. The antibody of claim 2, wherein the antibody is humanized.

9. The antibody of claim 2, wherein the antibody is produced by a hybridoma.

10. The antibody of claim 9, wherein the antibody has been humanized.