B7-H3L cell surface antigen and antibodies that bind thereto

• US 9,574,007 B2
• Filed: 06/03/2014
• Issued: 02/21/2017
• Est. Priority Date: 06/19/2002
• Status: Expired due to Term

• Current Assignee: MacroGenics, Inc.
• Original Assignee: MacroGenics, 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:
  US14/294,935
• Publication Number:
  US 20140328857A1
• Time in Patent Office: 994 Days
• Field of Search: None
• US Class Current: 1/1
• 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 method of treating cancer in a subject having a cancer comprising administering to the subject a composition comprising a therapeutically effective amount of an immunoglobulin polypeptide or an antigen-binding fragment thereof associated with a chemotherapeutic agent, wherein:

said immunoglobulin polypeptide or antigen-binding fragment thereof specifically binds to an epitope of a B7-H3L protein that is expressed and exposed in its native conformation on the surface of a cancer cell of said cancer, wherein said epitope is insufficiently expressed on the surface of a living normal cell to exhibit binding by said immunoglobulin polypeptide;

said immunoglobulin polypeptide or antigen-binding fragment thereof can be internalized into said cancer cell expressing B7-H3L; and

said immunoglobulin polypeptide or antigen-binding fragment thereof comprises the amino acid sequences of complementarity determining regions of 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.

2. The method 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. The method of claim 1, wherein said immunoglobulin polypeptide is a 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. The method of claim 1, wherein said chemotherapeutic agent is delivered into said cancer cell.

5. The method of claim 1, wherein the composition comprises an additional therapeutic moiety.

6. The method of claim 1, further comprising the administration of one or more additional cancer therapies.

7. The method of claim 6, wherein said additional cancer therapy is selected from the group consisting of chemotherapy, radiation therapy, and surgery.

8. The method of claim 1, wherein said administered composition increases antibody-dependent cell mediated cytotoxicity (ADCC).

9. The method of claim 1, wherein said subject is a human.

10. A method for delivering a chemotherapeutic agent to a cancer cell comprising administering to a subject a composition comprising a therapeutically effective amount of an immunoglobulin polypeptide or an antigen-binding fragment thereof associated with the chemotherapeutic agent, wherein:

said immunoglobulin polypeptide or antigen-binding fragment thereof specifically binds to an epitope of a B7-H3L protein that is expressed and exposed in its native conformation on the surface of the cancer cell, wherein said epitope is insufficiently expressed on the surface of a living normal cell to exhibit binding by said immunoglobulin polypeptide;

said immunoglobulin polypeptide or antigen-binding fragment thereof can be internalized into said cancer cell expressing B7-H3L; and

said immunoglobulin polypeptide or antigen-binding fragment thereof comprises the amino acid sequences of complementarity determining regions of 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.

11. The method of claim 10, 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.

12. The method of claim 10, wherein said immunoglobulin polypeptide is a 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.

13. The method of claim 10, wherein said chemotherapeutic agent is delivered into said cancer cell.

14. The method of claim 10, wherein the composition comprises an additional therapeutic moiety.

15. The method of claim 10, wherein said administered composition increases antibody-dependent cell mediated cytotoxicity (ADCC).

16. The method of claim 10, wherein said subject is a human.