Downmodulating an immune response with multivalent antibodies to PD-1

• US 6,808,710 B1
• Filed: 08/23/2000
• Issued: 10/26/2004
• Est. Priority Date: 08/23/1999
• Status: Expired due to Term

• Current Assignee: Dana-Farber Cancer Institute, Genetics Institute LLC (Pfizer Inc.)
• Original Assignee: Dana-Farber Cancer Institute, Genetics Institute LLC (Pfizer Inc.)
• Inventors: Wood, Clive, Freeman, Gordon J.
• Primary Examiner(s): Gambel, Phillip
• Assistant Examiner(s): ROARK, JESSICA HOPE
• Application Number:
  US09/645,069
• Time in Patent Office: 1,525 Days
• Field of Search: 530/387.1, 530/387.5, 530/387.9, 530/388.1, 530/388.2, 530/388.22, 530/388.7, 530/388.73, 530/388.75, 530/350, 424/130.1, 424/137.1, 424/139.1, 424/141.1, 424/143.1, 424/144.1, 424/152.1, 424/153.1, 424/154.1, 424/172.1, 424/173.1, 424/184.1
• US Class Current: 424/144.1
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 15/06 Antiabortive agents; Labour repressants
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 25/28 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/06 for tuberculosis
• 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 31/22 for herpes viruses
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 33/12 : Schistosomicides
• 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 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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: C07K 14/70503 : Immunoglobulin superfamily
• CPC Class Codes: C07K 14/70532 : B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 16/2803 : against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2827 : against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/74 : Inducing cell proliferation
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• 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
• CPC Class Codes: G01N 2333/70503 : Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
• CPC Class Codes: G01N 2500/04 : Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)

Abstract

The invention identifies PD-1 as a receptor for B7-4. B7-4 can inhibit immune cell activation upon binding to an inhibitory receptor on an immune cell. Accordingly, the invention provides agents for modulating PD-1, B7-4, and the interaction between B7-4 and PD-1 in order to modulate a costimulatory or an inhibitory signal in a immune cell resulting in modulation of the immune response.

Claims

1. A method for downmodulating an immune response comprising contacting an immune cell expressing PD-1 with an agent that binds to PD-1, wherein the agent comprises an antibody to PD-1 in multivalent form, such that a negative signal is transduced via PD-1 to thereby downmodulate the immune response.

2. The method of claim 1, wherein the agent further comprises a binding specificity for an activating receptor on the immune cell.

3. The method of claim 1, wherein the immune cell is selected from the group consisting of:

a T cell, a B cell, and a myeloid cell.

4. The method of claim 2, wherein anergy is induced in the immune cell.

5. The method of claim 2, further comprising contacting the immune cell with an additional agent that downregulates an immune response.

6. The method of claim 1, wherein the step of contacting occurs in vivo.

7. The method of claim 1, wherein the step of contacting occurs in vitro.

8. The method of claim 1, wherein the agent is a cross-linked antibody to PD-1.

9. The method of claim 1, wherein the agent comprises an immobilized antibody to PD-1.