Toll like receptor 3 antagonists, methods and uses

• US 8,153,583 B2
• Filed: 11/30/2005
• Issued: 04/10/2012
• Est. Priority Date: 11/30/2004
• Status: Active Grant

• Current Assignee: Anuk Das, David M. Knight, Gopalan Raghunathan, Jill M. Carton, Jill M. Giles-Komar, Karen Duffy, Kristen Picha, Lani San Mateo, Mark Cunningham, Mouhamadou L. Mbow, Nicole Stowell, Raymond Sweet, Roberta Lamb, Robert T. Sarisky, Shanrong Zhao, Shizhong Chen, Theresa J. Goletz, Vedrana Stojanovic-Susulic
• Original Assignee: Anuk Das, David M. Knight, Gopalan Raghunathan, Jill M. Carton, Jill M. Giles-Komar, Karen Duffy, Kristen Picha, Lani San Mateo, Mark Cunningham, Mouhamadou L. Mbow, Nicole Stowell, Raymond Sweet, Roberta Lamb, Robert T. Sarisky, Shanrong Zhao, Shizhong Chen, Theresa J. Goletz, Vedrana Stojanovic-Susulic
• Inventors: Carton, Jill M., Chen, Shizhong, Cunningham, Mark, Das, Anuk, Duffy, Karen, Giles-Komar, Jill M., Goletz, Theresa J., Knight, David M., Lamb, Roberta, Mbow, Mouhamadou L., Picha, Kristen, Raghunathan, Gopalan, San Mateo, Lani, Sarisky, Robert T., Stojanovic-Susulic, Vedrana, Stowell, Nicole, Sweet, Raymond, Zhao, Shanrong
• Primary Examiner(s): Landsman, Robert
• Assistant Examiner(s): DANG, IAN D
• Application Number:
  US11/291,140
• Publication Number:
  US 20060115475A1
• Time in Patent Office: 2,323 Days
• Field of Search: None
• US Class Current: 514/1.4
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• 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 19/10 for osteoporosis
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• 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 3/06 : Antihyperlipidemics
• 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 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• 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 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 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine 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 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07K 16/2896 : against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 : 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 2317/76 : 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

Toll Like Receptor 3 (TLR3) antagonists, polynucleotides encoding TLR3 antagonists, and methods of making and using the foregoing are disclosed.

Claims

1. A method of treating an inflammatory condition comprising administering a therapeutically effective amount of a Toll Like Receptor 3 (TLR3) antagonist antibody to a patient in need thereof for a time sufficient to treat the inflammatory condition wherein the TLR3 antagonist antibody is an isolated antibody reactive with TLR3 comprising the amino acid sequences of the heavy chain complementarity determining regions (CDRs) of SEQ ID NOs:

9, 11 and 13 and the amino acid sequences of the light chain CDRs of SEQ ID NOs;

19, 21 and 23.

2. The method of claim 1 wherein the inflammatory condition is a sepsis-associated condition.

3. The method of claim 1 wherein the inflammatory condition is an inflammatory bowel disease.

4. The method of claim 1 wherein the inflammatory condition is an infection-associated condition.

5. The method of claim 1 wherein the inflammatory condition is an inflammatory pulmonary condition.

6. The method of claim 1 wherein the inflammatory condition is type 2 diabetes, dislipidemia or metabolic syndrome.

7. The method of claim 1 wherein the inflammatory condition is caused by an autoimmune disease.

9. The method of claim 1 or 8 wherein the isolated antibody comprises a variable heavy chain (V_H) having the amino acid sequence shown in SEQ ID NO:

6, 25, 27, 29 or 31 and a variable light chain (V_L) chain having the amino acid sequence shown in SEQ ID NO;

16, 33, 35, 37 or 39.

8. A method of treating condition resulting from inflammation-induced cell death comprising administering a therapeutically effective amount of a TLR3 antibody antagonist to a patient in need thereof for a time sufficient to treat the condition wherein the TLR3 antagonist antibody is an isolated antibody reactive with TLR3 comprising the amino acid sequences of the heavy chain complementarity determining regions (CDRs) of SEQ ID NOs:

9, 11 and 13 and the amino acid sequences of the light chain CDRs of SEQ ID NOs;

19, 21 and 23.