Claims for Patent: 9,265,825

Summary for Patent: 9,265,825

Title:	Antagonists of IL-6 to raise albumin and/or lower CRP
Abstract:	The present invention is directed to therapeutic methods using IL-6 antagonists such as antibodies and fragments thereof having binding specificity for IL-6 to improve survivability or quality of life of a patient in need thereof. In preferred embodiments, the anti-IL-6 antibodies will be humanized and/or will be aglycosylated. Also, in preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level or a reduced serum albumin level prior to treatment. In another preferred embodiment, the patient\'s Glasgow Prognostic Score will be increased and survivability will preferably be improved.
Inventor(s):	Smith; Jeffrey T. L. (Bellevue, WA)
Assignee:	ALDERBIO HOLDINGS LLC (Las Vegas, NV)
Application Number:	13/780,018
Patent Claims:	1. A method of improving survivability or quality of life of a patient in need thereof, comprising administering to the patient an interleukin 6 (IL-6) antagonist, whereby (i) the patient's serum C-reactive protein ("CRP") level is reduced, and/or (ii) the patient's serum albumin level is increased, and further wherein the IL-6 antagonist comprises an anti-IL-6 antibody or antibody fragment which anti-IL-6 antibody, comprises a V.sub.L polypeptide comprising the CDR polypeptides of SEQ ID NO:103; SEQ ID NO: 104; and SEQ ID NO: 105 and a V.sub.H polypeptide comprising the CDR polypeptides of SEQ ID NO:106; SEQ ID NO: 107; and SEQ ID NO: 108, and wherein the administration of said antibody or antibody fragment improves the survivability or quality of life of the patient in need thereof by reducing the patient's serum C-reactive protein ("CRP") level and/or increasing the patient's serum albumin level. 2. The method of claim 1, wherein the administered antibody or antibody fragment comprising said CDRs polypeptides comprises V.sub.L and V.sub.H polypeptides respectively comprising at least 90% sequence identity to the amino acid sequences of SEQ ID NO:101 and SEQ ID NO:102. 3. The method of claim 2, wherein the V.sub.L and V.sub.H polypeptides of said anti-IL-6 antibody or antibody fragment comprise at least 95% sequence identity to V.sub.L and V.sub.H polypeptides respectively comprising the amino acid sequences of SEQ ID NO:101 and SEQ ID NO:102. 4. The method of claim 2, wherein the V.sub.L and V.sub.H polypeptides of said anti-IL-6 antibody or antibody fragment comprise at least 96% sequence identity to V.sub.L and V.sub.H polypeptides respectively comprising the amino acid sequences of SEQ ID NO:101 and SEQ ID NO:102. 5. The method of claim 2, wherein the V.sub.L and V.sub.H polypeptides of said anti-IL-6 antibody or antibody fragment comprise at least 97% sequence identity to V.sub.L and V.sub.H polypeptides respectively comprising the amino acid sequences of SEQ ID NO:101 and SEQ ID NO:102. 6. The method of claim 2, wherein the V.sub.L and V.sub.H polypeptides of said anti-IL-6 antibody or antibody fragment comprise at least 98% sequence identity to V.sub.L and V.sub.H polypeptides respectively comprising the amino acid sequences of SEQ ID NO:101 and SEQ ID NO:102. 7. The method of claim 2, wherein the V.sub.L and V.sub.H polypeptides of said anti-IL-6 antibody or antibody fragment comprise at least 99% sequence identity to V.sub.L and V.sub.H polypeptides respectively comprising the amino acid sequences of SEQ ID NO:101 and SEQ ID NO:102. 8. The method of claim 2, wherein the V.sub.L and V.sub.H polypeptides of said anti-IL-6 antibody or antibody fragment comprise 100% sequence identity to V.sub.L and V.sub.H polypeptides respectively comprising the amino acid sequences of SEQ ID NO:101 and SEQ ID NO:102. 9. The method of claim 1 wherein said patient has (i) an elevated serum CRP level prior to treatment, and/or (ii) a reduced serum albumin level prior to treatment. 10. The method of claim 1 whereby the patient's Glasgow Prognostic Score (GPS) is improved. 11. The method of claim 1 wherein the anti-IL-6 antibody further comprises the heavy chain and light chain constant regions comprised in the amino acid sequence of SEQ ID NO:588 and SEQ ID NO:586 respectively. 12. The method of claim 1, wherein the anti-IL-6 antibody or antibody fragment is aglycosylated and/or the anti-IL-6 antibody or antibody fragment contains an Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation. 13. The method of claim 1, wherein the anti-IL-6 antibody or antibody fragment is a human, humanized, single chain or chimeric antibody. 14. The method of claim 1 wherein the anti-IL-6 antibody or antibody fragment is administered to the patient with a frequency selected from (i) at most once per period of approximately four weeks, (ii) at most once per period of approximately eight weeks, (iii) at most once per period of approximately twelve weeks, or (iv) at most once per period of approximately sixteen weeks. 15. The method of claim 1 wherein the patient has been diagnosed with a cancer selected from Acanthoma, Acinic cell carcinoma, Acoustic neuroma, Acral lentiginous melanoma, Acrospiroma, Acute eosinophilic leukemia, Acute lymphoblastic leukemia, Acute megakaryoblastic leukemia, Acute monocytic leukemia, Acute myeloblastic leukemia with maturation, Acute myeloid dendritic cell leukemia, Acute myeloid leukemia, Acute promyelocytic leukemia, Adamantinoma, Adenocarcinoma, Adenoid cystic carcinoma, Adenoma, Adenomatoid odontogenic tumor, Adrenocortical carcinoma, Adult T-cell leukemia, Aggressive NK-cell leukemia, AIDS-Related Cancers, AIDS-related lymphoma, Alveolar soft part sarcoma, Ameloblastic fibroma, Anal cancer, Anaplastic large cell lymphoma, Anaplastic thyroid cancer, Angioimmunoblastic T-cell lymphoma, Angiomyolipoma, Angiosarcoma, Appendix cancer, Astrocytoma, Atypical teratoid rhabdoid tumor, Basal cell carcinoma, Basal-like carcinoma, B-cell leukemia, B-cell lymphoma, Bellini duct carcinoma, Biliary tract cancer, Bladder cancer, Blastoma, Bone Cancer, Bone tumor, Brain Stem Glioma, Brain Tumor, Breast Cancer, Brenner tumor, Bronchial Tumor, Bronchioloalveolar carcinoma, Brown tumor, Burkitt's lymphoma, Cancer of Unknown Primary Site, Carcinoid Tumor, Carcinoma, Carcinoma in situ, Carcinoma of the penis, Carcinoma of Unknown Primary Site, Carcinosarcoma, Castleman's Disease, Central Nervous System Embryonal Tumor, Cerebellar Astrocytoma, Cerebral Astrocytoma, Cervical Cancer, Cholangiocarcinoma, Chondroma, Chondrosarcoma, Chordoma, Choriocarcinoma, Choroid plexus papilloma, Chronic Lymphocytic Leukemia, Chronic monocytic leukemia, Chronic myelogenous leukemia, Chronic Myeloproliferative Disorder, Chronic neutrophilic leukemia, Clear-cell tumor, Colon Cancer, Colorectal cancer, Craniopharyngioma, Cutaneous T-cell lymphoma, Degos disease, Dermatofibrosarcoma protuberans, Dermoid cyst, Desmoplastic small round cell tumor, Diffuse large B cell lymphoma, Dysembryoplastic neuroepithelial tumor, Embryonal carcinoma, Endodermal sinus tumor, Endometrial cancer, Endometrial Uterine Cancer, Endometrioid tumor, Enteropathy-associated T-cell lymphoma, Ependymoblastoma, Ependymoma, Epithelioid sarcoma, Erythroleukemia, Esophageal cancer, Esthesioneuroblastoma, Ewing Family of Tumor, Ewing Family Sarcoma, Ewing's sarcoma, Extracranial Germ Cell Tumor, Extragonadal Germ Cell Tumor, Extrahepatic Bile Duct Cancer, Extramammary Paget's disease, Fallopian tube cancer, Fetus in fetu, Fibroma, Fibrosarcoma, Follicular lymphoma, Follicular thyroid cancer, Gallbladder Cancer, Ganglioglioma, Ganglioneuroma, Gastric Cancer, Gastric lymphoma, Gastrointestinal cancer, Gastrointestinal Carcinoid Tumor, Gastrointestinal Stromal Tumor, Germ cell tumor, Germinoma, Gestational choriocarcinoma, Gestational Trophoblastic Tumor, Giant cell tumor of bone, Glioblastoma multiforme, Glioma, Gliomatosis cerebri, Glomus tumor, Glucagonoma, Gonadoblastoma, Granulosa cell tumor, Hairy Cell Leukemia, Head and neck cancer, Heart cancer, Hemangioblastoma, Hemangiopericytoma, Hemangiosarcoma, Hematological malignancy, Hepatocellular carcinoma, Hepatosplenic T-cell lymphoma, Hereditary breast-ovarian cancer syndrome, Hodgkin's lymphoma, Hypopharyngeal Cancer, Hypothalamic Glioma, Inflammatory breast cancer, Intraocular Melanoma, Islet Cell Tumor, Juvenile myelomonocytic leukemia, Kaposi's sarcoma, Kidney Cancer, Klatskin tumor, Krukenberg tumor, Laryngeal Cancer, Lentigo maligna melanoma, Leukemia, Lip and Oral Cavity Cancer, Liposarcoma, Lung cancer, Luteoma, Lymphangioma, Lymphangiosarcoma, Lymphoepithelioma, Lymphoid leukemia, Lymphoma, Macroglobulinemia, Malignant Fibrous Histiocytoma, Malignant Fibrous Histiocytoma of Bone, Malignant Glioma, Malignant Mesothelioma, Malignant peripheral nerve sheath tumor, Malignant rhabdoid tumor, Malignant triton tumor, MALT lymphoma, Mantle cell lymphoma, Mast cell leukemia, Mediastinal germ cell tumor, Mediastinal tumor, Medullary thyroid cancer, Medulloblastoma, Medulloepithelioma, Melanoma, Meningioma, Merkel Cell Carcinoma, Mesothelioma, Metastatic Squamous Neck Cancer with Occult Primary, Metastatic urothelial carcinoma, Mixed Mullerian tumor, Monocytic leukemia, Mouth Cancer, Mucinous tumor, Multiple Endocrine Neoplasia Syndrome, Multiple myeloma, Mycosis Fungoides, Myelodysplastic Disease, Myelodysplastic Syndromes, Myeloid leukemia, Myeloid sarcoma, Myeloproliferative Disease, Myxoma, Nasal Cavity Cancer, Nasopharyngeal Cancer, Nasopharyngeal carcinoma, Neoplasm, Neurinoma, Neuroblastoma, Neurofibroma, Neuroma, Nodular melanoma, Non-Hodgkin lymphoma, Nonmelanoma Skin Cancer, Non-Small Cell Lung Cancer, Ocular oncology, Oligoastrocytoma, Oligodendroglioma, Oncocytoma, Optic nerve sheath meningioma, Oral cancer, Oropharyngeal Cancer, Osteosarcoma, Ovarian Cancer, Ovarian Epithelial Cancer, Ovarian Germ Cell Tumor, Ovarian Low Malignant Potential Tumor, Paget's disease of the breast, Pancoast tumor, Pancreatic Cancer, Papillary thyroid cancer, Papillomatosis, Paraganglioma, Paranasal Sinus Cancer, Parathyroid Cancer, Penile Cancer, Perivascular epithelioid cell tumor, Pharyngeal Cancer, Pheochromocytoma, Pineal Parenchymal Tumor of Intermediate Differentiation, Pineoblastoma, Pituicytoma, Pituitary adenoma, Pituitary tumor, Plasma Cell Neoplasm, Pleuropulmonary blastoma, Polyembryoma, Precursor T-lymphoblastic lymphoma, Primary central nervous system lymphoma, Primary effusion lymphoma, Primary Hepatocellular Cancer, Primary Liver Cancer, Primary peritoneal cancer, Primitive neuroectodermal tumor, Prostate cancer, Pseudomyxoma peritonei, Rectal Cancer, Renal cell carcinoma, Respiratory Tract Carcinoma Involving the NUT Gene on Chromosome 15, Retinoblastoma, Rhabdomyoma, Rhabdomyosarcoma, Richter's transformation, Sacrococcygeal teratoma, Salivary Gland Cancer, Sarcoma, Schwannomatosis, Sebaceous gland carcinoma, Secondary neoplasm, Seminoma, Serous tumor, Sertoli-Leydig cell tumor, Sex cord-stromal tumor, Sezary Syndrome, Signet ring cell carcinoma, Skin Cancer, Small blue round cell tumor, Small cell carcinoma, Small Cell Lung Cancer, Small cell lymphoma, Small intestine cancer, Soft tissue sarcoma, Somatostatinoma, Soot wart, Spinal Cord Tumor, Spinal tumor, Splenic marginal zone lymphoma, Squamous cell carcinoma, Stomach cancer, Superficial spreading melanoma, Supratentorial Primitive Neuroectodermal Tumor, Surface epithelial-stromal tumor, Synovial sarcoma, T-cell acute lymphoblastic leukemia, T-cell large granular lymphocyte leukemia, T-cell leukemia, T-cell lymphoma, T-cell prolymphocytic leukemia, Teratoma, Terminal lymphatic cancer, Testicular cancer, Thecoma, Throat Cancer, Thymic Carcinoma, Thymoma, Thyroid cancer, Transitional Cell Cancer of Renal Pelvis and Ureter, Transitional cell carcinoma, Urachal cancer, Urethral cancer, Urogenital neoplasm, Uterine sarcoma, Uveal melanoma, Vaginal Cancer, Verner Morrison syndrome, Verrucous carcinoma, Visual Pathway Glioma, Vulvar Cancer, Waldenstrom's macroglobulinemia, Warthin's tumor, Wilms' tumor, or any combination thereof. 16. The method of claim 1 wherein said anti-IL-6 antibody or antibody fragment comprises a human Fc derived from IgG1, IgG2, IgG3, or IgG4. 17. The method of claim 1 wherein the anti-IL-6 antibody or antibody fragment is co-administered with another therapeutic agent. 18. The method of claim 17 wherein the other therapeutic agent is selected from VEGF antagonists, EGFR antagonists, platins, taxols, irinotecan, 5-fluorouracil, gemcytabine, leucovorine, steroids, cyclophosphamide, melphalan, vinca alkaloids, mustines, tyrosine kinase inhibitors, radiotherapy, sex hormone antagonists, selective androgen receptor modulators, selective estrogen receptor modulators, PDGF antagonists, TNF antagonists, IL-1 antagonists, interleukins, IL-12R antagonists, Toxin conjugated monoclonal antibodies, tumor antigen specific monoclonal antibodies, Erbitux.TM., Avastin.TM., Pertuzumab, anti-CD20 antibodies, Rituxan.TM., ocrelizumab, ofatumumab, DXL625, Herceptin.TM., or any combination thereof, or comprises an inhibitor of JAK1, JAK2, JAK3, or SYK. 19. The method of claim 1, wherein the anti-IL-6 antibody or fragment inhibits the binding of IL-6 to gp130 and IL-6R1.

Details for Patent 9,265,825

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Novartis Pharmaceuticals Corporation	ARZERRA	ofatumumab	Injection	125326	10/26/2009		2028-11-25
Novartis Pharmaceuticals Corporation	ARZERRA	ofatumumab	Injection	125326	04/01/2011		2028-11-25
Novartis Pharmaceuticals Corporation	KESIMPTA	ofatumumab	Injection	125326	08/20/2020		2028-11-25
Genentech, Inc.	PERJETA	pertuzumab	Injection	125409	06/08/2012		2028-11-25
Genentech, Inc.	OCREVUS	ocrelizumab	Injection	761053	03/28/2017		2028-11-25