B7-H3L cell surface antigen and antibodies that bind thereto

• US 8,779,098 B2
• Filed: 03/27/2009
• Issued: 07/15/2014
• Est. Priority Date: 06/19/2002
• Status: Active Grant

• Current Assignee: MacroGenics, Inc.
• Original Assignee: Macrogenics West, Inc.
• Inventors: Mather, Jennie P., Li, Ronghao, Pan, Zhuangyu, Roberts, Penelope E.
• Primary Examiner(s): Goddard, Laura B
• Assistant Examiner(s): Natarajan, Meera
• Application Number:
  US12/413,483
• Publication Number:
  US 20090202561A1
• Time in Patent Office: 1,936 Days
• Field of Search: None
• US Class Current: 530/387.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: A61N 5/10 X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy A61N5/01 takes precedence
• 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 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 17/06 Antipsoriatics
• 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 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 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 14/70532 : B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 16/2827 : against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 16/30 : from tumour cells
• CPC Class Codes: C07K 2317/77 : Internalization into the cell
• CPC Class Codes: G01N 2333/70503 : Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
• CPC Class Codes: G01N 33/57492 : involving compounds localized on the membrane of tumor or cancer cells

Abstract

The invention provides the identification and characterization of disease and cancer-associated antigen, RAAG10. The invention also provides a family of monoclonal antibodies that bind to antigen RAAG10, methods of diagnosing and treating various human cancers and diseases that express RAAG10.

Claims

1. A substantially purified immunoglobulin polypeptide or an antigen binding fragment thereof, that specifically binds to an epitope of a B7-H3L protein that is expressed and exposed in its native conformation on the surface of a living cancer cell in vitro or in vivo, wherein said epitope is insufficiently expressed on the surface of a living normal cell to exhibit binding by said purified immunoglobulin polypeptide, and wherein said purified immunoglobulin polypeptide or antigen binding fragment thereof can be internalized into said cancer cell expressing B7-H3L.

2. The purified immunoglobulin polypeptide or antigen binding fragment of claim 1, wherein said cancer cell is selected from the group consisting of a cancer cell from:

an adrenal gland tumor, an AIDS-associated cancer, an alveolar soft part sarcoma, an astrocytic tumor, a bladder cancer, a bone cancer, a brain or spinal cord cancer, a metastatic brain tumor, a breast cancer, a carotid body tumor, a cervical cancer, a chondrosarcoma, a chordoma, a chromophobe renal cell carcinoma, a clear cell carcinoma, a colon cancer, a colorectal cancer, a cutaneous benign fibrous histiocytoma, a desmoplastic small round cell tumor, an ependymoma, a Ewing'"'"'s tumor, an extraskeletal myxoid chondrosarcoma, a fibrogenesis imperfecta ossium, a fibrous dysplasia of the bone, a gallbladder or bile duct cancer, a gestational trophoblastic disease, a germ cell tumor, a head and neck cancer, an islet cell tumor, a Kaposi'"'"'s Sarcoma, a kidney cancer, a leukemia, a lipoma/benign lipomatous tumor, a liposarcoma/malignant lipomatous tumor, a liver cancer, a lymphoma, a lung cancer, a medulloblastoma, a melanoma, a meningioma, a multiple endocrine neoplasia, a multiple myeloma, a myelodysplastic syndrome cell, a neuroblastoma, a neuroendocrine tumor, an ovarian cancer, a pancreatic cancer, a papillary thyroid carcinoma, a parathyroid tumor, a pediatric cancer cell, a peripheral nerve sheath tumor, a phaeochromocytoma, a pituitary tumor, a prostate cancer, a posterious uveal melanoma, a rare hematologic disorder, a renal metastatic cancer, a rhabdoid tumor, a rhabdomysarcoma, a sarcoma, a skin cancer, a soft-tissue sarcoma a squamous cell cancer, a stomach cancer, a synovial sarcoma, a testicular cancer, a thymic carcinoma, a thymoma, a thyroid metastatic cancer, and a uterine cancer.

3. A pharmaceutical composition comprising the purified immunoglobulin polypeptide or antigen binding fragment of claim 1, together with a pharmaceutically acceptable carrier.

7. The purified immunoglobulin polypeptide or antigen binding fragment of claim 1, wherein said purified immunoglobulin polypeptide or antigen binding fragment thereof exhibits the same binding specificity as the monoclonal antibody expressed by the hybridoma having ATCC Deposit No. PTA-4217, ATCC Deposit No. PTA-4218, ATCC Deposit No. PTA-4244, or ATCC Deposit No. PTA-4245.

4. A pharmaceutical composition comprising a monoclonal antibody or an antigen binding fragment thereof that specifically binds to an epitope of B7-H3L protein that is expressed and exposed in its native conformation on the surface of a living cancer cell in vitro or in vivo, wherein said epitope is insufficiently expressed on the surface of a living normal cell to exhibit binding by said antibody, and wherein said purified antibody or antigen binding fragment thereof can be internalized into said cancer cell expressing B7-H3L;

together with a pharmaceutically acceptable carrier.

5. The pharmaceutical composition of claim 4, wherein the composition comprises an additional therapeutic moiety.

6. An isolated antibody comprising an antigen-binding fragment of the antibody expressed by the hybridoma having ATCC Deposit No. PTA-4217, ATCC Deposit No. PTA-4218, ATCC Deposit No. PTA-4244, or ATCC Deposit No. PTA-4245.