Claims for Patent: 10,233,228

Summary for Patent: 10,233,228

Title:	Albumin derivatives and variants
Abstract:	The application discloses albumin derivatives comprising or consisting of domain III and at least one further domain wherein the derivative or variant is not a naturally occurring albumin derivative or variant. The derivatives may be used in conjugates and fusion polypeptides.
Inventor(s):	Plumridge; Andrew (Derbyshire, GB), Sleep; Darrell (Nottingham, GB), Sandlie; Inger (Oslo, NO), Andersen; Jan Terje (Oslo, NO), Cameron; Jason (Nottingham, GB), Evans; Leslie (Nottingham, GB), Athwal; Steven (Nottingham, GB), Allan; Elizabeth (Nottingham, GB), Friis; Esben Peter (Herlev, DK)
Assignee:	ALBUMEDIX LTD (Nottingham, GB)
Application Number:	13/640,235
Patent Claims:	1. An albumin derivative or variant, fragment thereof or fusion polypeptide comprising said albumin derivative or variant or fragment thereof wherein the albumin derivative or variant or fragment thereof has a molecular weight from 40 to 91 kDA, and comprises: (i) a first albumin domain III or a derivative or variant thereof having at least 90% sequence identity to human serum albumin (HSA) domain III; and (ii) a second albumin domain III or a derivative or variant thereof having at least 90% identity to human serum albumin (HSA) domain III. 2. The albumin derivative or variant, fragment thereof or fusion polypeptide of claim 1, wherein the first and/or second albumin domain III or derivative or variant thereof is derived, independently, from human serum albumin, chimpanzee serum albumin, or macaque serum albumin. 3. The albumin derivative or variant, fragment thereof or fusion polypeptide of claim 1, wherein the first and/or second albumin domain III or derivative or variant thereof has at least 95% sequence identity to Domain III of SEQ ID NO: 31 or SEQ ID NO: 1. 4. The albumin derivative or variant, fragment thereof or fusion polypeptide of claim wherein the Domain III or derivative or variant thereof has at least 95% sequence identity to amino acids 381 to 585 of SEQ ID NO: 31 or SEQ ID NO: 1. 5. The albumin derivative or variant, fragment thereof or fusion polypeptide according to claim 1 in which the albumin derivative or variant, fragment thereof or fusion polypeptide comprises two copies of human serum albumin domain III. 6. The albumin derivative or variant, fragment thereof or fusion polypeptide according to claim 1, wherein at least one domain III comprises one or more substitutions in positions corresponding to the positions in SEQ ID NO: 31 or SEQ ID NO:1 (HSA) selected from: 573, 500, 550, 417, 440, 464, 490, 492, 493, 494, 495, 496, 499, 501, 503, 504, 505, 506, 510, 535, 536, 537, 538, 540, 541, 542, 574, 575, 577, 578, 579, 580, 581, 582 or 584. 7. The albumin derivative or variant, fragment thereof or fusion polypeptide according to claim 6, wherein the one or more substitutions in positions corresponding to the positions in SEQ ID NO: 31 or SEQ ID NO:1 (HSA) is selected from: K573P, K573Y, K573W, K573H, K573F, K573V, K573I, K573T, K573N, K573S, K573G, K573M, K573C, K573A, K573E, K573Q, K573R, K573L, K573D, K500E, K500G, K500D, K500A, K500S, K500C, K500P, K500H, K500F, K500N, K500W, K500T, K500M, K500Y, K500V, K500Q, K500L, K500I, K500R Q417A, H440A, H464Q, E492G, D494N, D494Q, D494A, E495Q, E495A, T496A, D494E+Q417H, D494N+T496A, E492G+V493P, P499A, E501A, E501Q, N503H, N503K, H510Q, H535Q, K536A, P537A, K538A, K541G, K541D, D550E, D550N, E492G+K573P, E492G+K573A, or E492G+N503H+K573P/N503H/K573P. 8. The albumin derivative or variant, fragment thereof or fusion polypeptide according to claim 1, comprising one or more additional mutations that creates one or more thiol groups on the surface of the molecule. 9. The albumin derivative or variant, fragment thereof or fusion polypeptide according to claim 8, having a substitution selected from the group of substitutions corresponding to: L585C, D1C, A2C, D562C, A364C, A504C, E505C, T79C, E86C, D129C, D549C, A581C, D121C, E82C, S270C, A578C, L595LC, D1DC, A2AC, D562DC, A364AC, A504AC, E505EC, T79TC, E86EC, D129DC, D549DC, A581AC, A581AC, D121DC, E82EC, S270SC, or A579AC, or a deletion at a position selected from the group corresponding to: C360, C316, C75, C168, C558, C361, C91, C124, C169 and or C567 in SEQ ID NO: 31 or SEQ ID NO: 1. 10. A conjugate comprising an albumin derivative or variant or fragment thereof according to claim 1, and a therapeutic or diagnostic moiety bound to the albumin part. 11. A pharmaceutical composition comprising: an albumin derivative, fragment thereof or fusion polypeptide or associate of claim 1. 12. An albumin variant according to claim 1, which albumin variant has (i) a longer plasma half-life than native HSA or (ii) a shorter plasma half-life than native HSA. 13. A fusion of an albumin variant according to claim 1, which fusion has (i) a longer plasma half-life than an albumin fusion, conjugate, associate or composition comprising native HSA or (ii) a shorter than a fusion, conjugate, associate or composition comprising native HSA. 14. A fusion of an albumin variant according to claim 1 wherein the fusion comprises one or more moiety selected from the group consisting of: 4-1BB ligand, 5-helix, A human C-C chemokine, A human L105 chemokine, A human L105 chemokine designated huL105_3, A monokine induced by gamma-interferon, A partial CXCR4B protein, A platelet basic protein, .alpha.1-antitrypsin, ACRP-30 Homologue, Complement Component C1q C, Adenoid-expressed chemokine, aFGF, FGF-1, AGF, AGF Protein, albumin, an etoposide, angiostatin, Anthrax vaccine, Antibodies specific for collapsin, antistasin, Anti-TGF beta family antibodies, antithrombin III, APM-1, ACRP-30, Famoxin, apo-lipoprotein species, Arylsulfatase B, b57 Protein, BCMA, Beta-thromboglobulin protein, bFGF, FGF2, Blood coagulation factors, BMP Processing Enzyme Furin, BMP-10, BMP-12, BMP-15, BMP-17, BMP-18, BMP-2B, BMP-4, BMP-5, BMP-6, BMP-9, Bone Morphogenic Protein-2, calcitonin, Calpain-10a, Calpain-10b, Calpain-10c, Cancer Vaccine, Carboxypeptidase, C-C chemokine, MCP2, CCR5 variant, CCR7, CCR7, CD11a Mab, CD137; 4-1BB Receptor Protein, CD20 Mab, CD27, CD27L, CD30, CD30 ligand, CD33 immunotoxin, CD40, CD40L, CD52 Mab, Cerebus Protein, Chemokine Eotaxin, Chemokine hIL-8, Chemokine hMCP1, Chemokine hMCP1a, Chemokine hMCP1b, Chemokine hMCP2, Chemokine hMCP3, Chemokine hSDF1b, Chemokine MCP-4, chemokine TECK and TECK variant, Chemokine-like protein IL-8M1 Full-Length and Mature, Chemokine-like protein IL-8M10 Full-Length and Mature, Chemokine-like protein IL-8M3, Chemokine-like protein IL-8M8 Full-Length and Mature, Chemokine-like protein IL-8M9 Full-Length and Mature, Chemokine-like protein PF4-414 Full-Length and Mature, Chemokine-like protein PF4-426 Full-Length and Mature, Chemokine-like protein PF4-M2 Full-Length and Mature, Cholera vaccine, Chondromodulin-like protein, c-kit ligand, SCF, Mast cell growth factor, MGF, Fibrosarcoma-derived stem cell factor, CNTF and fragment thereof, coagulation factors in both pre and active forms, collagens, Complement C5 Mab, Connective tissue activating protein-III, CTAA16.88 Mab, CTAP-III, CTLA4-Ig, CTLA-8, CXC3, CXC3, CXCR3, CXC chemokine receptor 3, cyanovirin-N, Darbepoetin, designated exodus, designated huL105_7, DIL-40, Dnase, EDAR, EGF Receptor Mab, ENA-78, Endostatin, Eotaxin, Epithelial neutrophil activating protein-78, EPO receptor, EPOR, erythropoietin, EPO mimics, Eutropin, Exodus protein, Factor IX, Factor VII, Factor VIII, Factor X, Factor XIII, FAS Ligand Inhibitory Protein, FasL, FasL, FasL, FGF, FGF-12, Fibroblast growth factor homologous factor-1, FGF-15, FGF-16, FGF-18, FGF-3, INT-2, FGF-4, gelonin, HST-1, HBGF-4, FGF-5, FGF-6, Heparin binding secreted transforming factor-2, FGF-8, FGF-9, Glia activating factor, fibrinogen, flt-1, flt-3 ligand, Follicle stimulating hormone Alpha subunit, Follicle stimulating hormone Beta subunit, Follitropin, Fractalkine, myofibrillar protein Troponin I, FSH, Galactosidase, Galectin-4, G-CSF, GDF-1, Gene therapy, Glioma-derived growth factor, glucagon, glucagon-like peptides, Glucocerebrosidase, glucose oxidase, Glucosidase, Glycodelin-A, Progesterone-associated endometrial protein, GM-CSF, gonadotropin, Granulocyte chemotactic protein-2, Granulocyte-macrophage colony stimulating factor, growth hormone, Growth related oncogene-alpha, Growth related oncogene-beta, Growth related oncogene-gamma, hAPO-4, TROY, hCG, Hepatitus B surface Antigen, Hepatitus B Vaccine, HER2 Receptor Mab, hirudin, HIV gp120, HIV gp41, HIV Inhibitor Peptide, HIV Inhibitor Peptide, HIV Inhibitor Peptide, HIV protease inhibiting peptides, HIV-1 protease inhibitors, HPV vaccine, Human 6CKine protein, Human Act-2 protein, Human adipogenesis inhibitory factor, human B cell stimulating factor-2 receptor, Human beta-chemokine H1305, Human C-C chemokine DGWCC, Human CC chemokine ELC protein, Human CC type chemokine interleukin C, Human CCC3 protein, Human CCF18 chemokine, Human CC-type chemokine protein designated SLC, Human chemokine beta-8 short forms, Human chemokine C10, Human chemokine CC-2, Human chemokine CC-3, Human chemokine CCR-2, Human chemokine Ckbeta-7, Human chemokine ENA-78, Human chemokine eotaxin, Human chemokine GRO alpha, Human chemokine GROalpha, Human chemokine GRObeta, Human chemokine HCC-1, Human chemokine HCC-1, Human chemokine 1-309, Human chemokine IP-10, Human chemokine L105_3, Human chemokine L105_7, Human chemokine MIG, Human chemokine MIG-beta protein, Human chemokine MIP-1 alpha, Human chemokine MIP1beta, Human chemokine MIP-3alpha, Human chemokine MIP-3beta, Human chemokine PF4, Human chemokine protein 331D5, Human chemokine protein 61164, Human chemokine receptor CXCR3, Human chemokine SDF1alpha, Human chemokine SDF1beta, Human chemokine ZSIG-35, Human Chr19Kine protein, Human CKbeta-9, Human CKbeta-9, Human CX3C 111 amino acid chemokine, Human DNAX interleukin-40, Human DVic-1 C-C chemokine, Human EDIRF I protein sequence, Human EDIRF II protein sequence, Human eosinocyte CC type chemokine eotaxin, Human eosinophil-expressed chemokine, Human fast twitch skeletal muscle troponin C, Human fast twitch skeletal muscle troponin I, Human fast twitch skeletal muscle Troponin subunit C, Human fast twitch skeletal muscle Troponin subunit I Protein, Human fast twitch skeletal muscle Troponin subunit T, Human fast twitch skeletal muscle troponin T, Human foetal spleen expressed chemokine, FSEC, Human GM-CSF receptor, Human gro-alpha chemokine, Human gro-beta chemokine, Human gro-gamma chemokine, Human IL-16 protein, Human IL-1RD10 protein sequence, Human IL-1RD9, Human IL-5 receptor alpha chain, Human IL-6 receptor, Human IL-8 receptor protein hIL8RA, Human IL-8 receptor protein hIL8RB, Human IL-9 receptor protein, Human IL-9 receptor protein variant #3, Human IL-9 receptor protein variant fragment, Human IL-9 receptor protein variant fragment#3, Human interleukin 1 delta, Human Interleukin 10, Human Interleukin 10, Human interleukin 18, Human interleukin 18 derivatives, Human interleukin-1 beta precursor, Human interleukin-1 beta precursor, Human interleukin-1 receptor accessory protein, Human interleukin-1 receptor antagonist beta, Human interleukin-1 type-3 receptor, Human Interleukin-10 precursor, Human Interleukin-10 precursor, Human interleukin-11 receptor, Human interleukin-12 40 kD subunit, Human interleukin-12 beta-1 receptor, Human interleukin-12 beta-2 receptor, Human Interleukin-12 p35 protein, Human Interleukin-12 p40 protein, Human interleukin-12 receptor, Human interleukin-13 alpha receptor, Human interleukin-13 beta receptor, Human interleukin-15, Human interleukin-15 receptor from clone P1, Human interleukin-17 receptor, Human interleukin-18 protein, Human interleukin-3, human interleukin-3 receptor, Human interleukin-3 variant, Human interleukin-4 receptor, Human interleukin-5, Human interleukin-6, Human interleukin-7, Human interleukin-7, Human interleukin-8, Human intracellular IL-1 receptor antagonist, Human IP-10 fusion protein, HIV-1 gp120 hypervariable region fusion protein, Human IP-10-human Muc-1 core epitope fusion protein, human liver--activation regulated chemokine, Human Lkn-1 Full-Length and Mature protein, Human mammary associated chemokine protein Full-Length and Mature, Human mature chemokine Ckbeta-7, Human mature gro-alpha, Human mature gro-gamma polypeptide used to treat sepsis, Human MCP-3 and human Muc-1 core epitope fusion protein, Human MI10 protein, Human MI1A protein, Human monocyte chemoattractant factor hMCP-1, Human monocyte chemoattractant factor hMCP-3, Human monocyte chemotactic proprotein sequence, Human neurotactin chemokine like domain, Human non-ELR CXC chemokine H174, Human non-ELR CXC chemokine IP10, Human non-ELR CXC chemokine Mig, Human PAI-1 mutants, Human protein with IL-16 activity, Human protein with IL-16 activity, Human secondary lymphoid chemokine, Human SISD protein, Human STCP-1, Human stromal cell-derived chemokine, SDF-1, Human T cell mixed lymphocyte reaction expressed chemokine, Human thymus and activation regulated cytokine, Human thymus expressed, Human TNF-alpha, Human TNF-alpha, Human TNF-beta, Human type CC chemokine eotaxin 3 protein sequence, Human type II interleukin-1 receptor, Human wild-type interleukin-4 protein, Human ZCHEMO-8 protein, Humanized Anti-VEGF Antibodies, Humanized Anti-VEGF Antibodies, Hyaluronidase, ICE 10 kD subunit, ICE 20 kD subunit, ICE 22 kD subunit, Iduronate-2-sulfatase, Iduronidase, IL-1 alpha, IL-1 beta, IL-1 inhibitor, IL-1 mature, IL-10 receptor, IL-11, IL-11, IL-12 p40 subunit, IL-13, IL-14, IL-15, IL-15 receptor, IL-17, IL-17 receptor, Il-17 receptor, 11-17 receptor, IL-19, IL-1i fragments, IL1-receptor antagonist, IL-21, IL-3 containing fusion protein, IL-3 mutant proteins, IL-3 variants, IL-3 variants, IL-4, IL-4 mutein, IL-4 mutein Y124G, IL-4 mutein Y124X, IL-4 muteins, 11-5 receptor, IL-6, 11-6 receptor, IL-7 receptor clone, IL-8 receptor, IL-9 mature protein variant, immunoglobulins or immunoglobulin-based molecules or fragment of either, dAb, Fab' fragments, F(ab')2, scAb, scFv, scFv fragment, plasminogen, Influenza Vaccine, Inhibin alpha, Inhibin beta, insulin, insulin-like growth factor, Integrin Mab, inter-alpha trypsin inhibitor, inter-alpha trypsin inhibitor, Interferon gamma-inducible protein, interferons, interferons, Interleukin 6, Interleukin 8 receptor, Interleukin 8 receptor B, Interleukin-1alpha, Interleukin-2 receptor associated protein p43, interleukin-3, interleukin-4 muteins, Interleukin-8 protein, interleukin-9, Interleukin-9 mature protein, interleukins, interleukins, Japanese encephalitis vaccine, Kalikrein Inhibitor, Keratinocyte growth factor, Kunitz domain protein, Kunitz domain protein, LACI, lactoferrin, Latent TGF-beta binding protein II, leptin, Liver expressed chemokine-1, Liver expressed chemokine-2, LT-alpha, LT-beta, Luteinization Hormone, Lyme Vaccine, Lymphotactin, Macrophage derived chemokine analogue MDC (n+1), Macrophage derived chemokine analogue MDC-eyfy, Macrophage derived chemokine analogue MDC-yl, Macrophage derived chemokine, MDC, Macrophage-derived chemokine, Maspin, Protease Inhibitor 5, MCP-1 receptor, MCP-1a, MCP-1b, MCP-3, MCP-4 receptor, M-CSF, Melanoma inhibiting protein, Membrane-bound proteins, Met117 human interleukin 9, MIP-3 alpha, MIP-3 beta, MIP-Gamma, MIRAP, Modified Rantes, monoclonal antibody, MP52, Mutant Interleukin 6 S176R, myofibrillar contractile protein Troponin I, Natriuretic Peptide, Nerve Growth Factor-beta, Nerve Growth Factor-beta2, Neuropilin-1, Neuropilin-2, Neurotactin, Neurotrophin-3, Neurotrophin-4, Neurotrophin-4a, Neurotrophin-4b, Neurotrophin-4c, Neurotrophin-4d, Neutrophil activating peptide-2, NOGO-66 Receptor, NOGO-A, NOGO-B, NOGO-C, Novel beta-chemokine designated PTEC, N-terminal modified chemokine GroHEK/hSDF-1alpha, N-terminal modified chemokine GroHEK/hSDF-1beta, N-terminal modified chemokine met-hSDF-1 alpha, N-terminal modified chemokine met-hSDF-1 beta, OPGL, Osteogenic Protein-1, OP-1, BMP-7, Osteogenic Protein-2, OX40, ACT-4, OX40L, Oxytocin, parathyroid hormone, Patched, Patched-2, PDGF-D, Pertussis toxoid, Pituitary expressed chemokine, Placental Growth Factor, Placental Growth Factor-2, Plasminogen Activator Inhibitor-1, PAI-1, Plasminogen Activator Inhibitor-2, PAI-2, Plasminogen Activator Inhibitor-2, PAI-2, Platelet derived growth factor, Platelet derived growth factor Bv-sis, Platelet derived growth factor precursor A, Platelet derived growth factor precursor B, Platelet Mab, platelet-derived endothelial cell growth factor, Platelet-Derived Growth Factor A chain, Platelet-Derived Growth Factor B chain, polypeptide used to treat sepsis, Preproapolipoprotein "milano" variant, Preproapolipoprotein "paris" variant, pre-thrombin, Primate CC chemokine "ILINCK", Primate CXC chemokine "IBICK", proinsulin, Prolactin, Prolactin2, prosaptide, Protease inhibitor peptides, Protein C, Protein S, pro-thrombin, prourokinase, RANTES, RANTES 8-68, RANTES 9-68, RANTES peptide, RANTES receptor, Recombinant interleukin-16, Resistin, restrictocin, Retroviral protease inhibitors, ricin, Rotavirus Vaccine, RSV Mab, saporin, sarcin, Secreted, polypeptides, Transmembrane polypeptides, Secreted and Transmembrane polypeptides, serum cholinesterase, serum protein, Soluble BMP Receptor Kinase Protein-3, Soluble VEGF Receptor, Stem Cell Inhibitory Factor, Straphylococcus Vaccine, Stromal Derived Factor-1 alpha, Stromal Derived Factor-1 beta, Substance P, T1249 peptide, T20 peptide, T4 Endonuclease, TACI, Tarc, TGF-beta 1, TGF-beta 2, Thr117 human interleukin 9, thrombin, thrombopoietin, Thrombopoietin derivative1, Thrombopoietin derivative2, Thrombopoietin derivative3, Thrombopoietin derivative4, Thrombopoietin derivative5, Thrombopoietin derivative6, Thrombopoietin derivative7, Thymus expressed chemokine, Thyroid stimulating Hormone, tick anticoagulant peptide, Tim-1 protein, TNF-alpha precursor, TNF-R, TNF-RII, TNF p75 Receptor, Death Receptor, tPA, transferrin, transforming growth factor beta, Troponin peptides, Truncated monocyte chemotactic protein 2, Truncated monocyte chemotactic protein 2, Truncated RANTES protein, tumour necrosis factor, Urate Oxidase, urokinase, Vasopressin, VEGF R-3, flt-4, VEGF Receptor, KDR, flk-1, VEGF-110, VEGF-121, VEGF-138, VEGF-145, VEGF-162, VEGF-165, VEGF-182, VEGF-189, VEGF-206, VEGF-D, VEGF-E, VEGF-X, von Willebrand's factor, Wild type monocyte chemotactic protein 2, Wild type monocyte chemotactic protein 2, and ZTGF-beta 9. 15. A fusion of an albumin variant according to claim 1 wherein the fusion comprises one or more moiety of chemotherapeutic drug or imaging agent. 16. The albumin derivative or variant, fragment thereof or fusion polypeptide according to claim 1 in which the albumin derivative or variant, fragment thereof or fusion polypeptide comprises two copies of human serum albumin domain III, the first copy having at least 95% sequence identity to amino acid residues 1 to 205 of SEQ ID NO: 24, and the second copy having at least 95% sequence identity to amino acid residues 1 to 205 of SEQ ID NO: 24. 17. The albumin derivative or variant, fragment thereof or fusion polypeptide according to claim 1 in which the albumin derivative or variant, fragment thereof or fusion polypeptide consists of two copies of human serum albumin domain III. 18. An albumin derivative or variant, fragment thereof or fusion polypeptide comprising said albumin derivative or variant or fragment thereof, wherein the albumin derivative or variant or fragment thereof comprises: (i) a first albumin domain III or a derivative or variant thereof having at least 90% sequence identity to human serum albumin (HSA) domain III; and (ii) a second albumin domain III or a derivative or variant thereof having at least 90% identity to human serum albumin (HSA) domain III; and wherein the albumin derivative or variant or fragment thereof contains not more than one copy of domain I or a derivative or variant thereof having at least 90% sequence identity to human serum albumin (HSA) domain I.

Details for Patent 10,233,228

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	05/05/2004		2030-04-09
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	12/02/2004		2030-04-09
Amphastar Pharmaceuticals, Inc.	AMPHADASE	hyaluronidase	Injection	021665	10/26/2004		2030-04-09
Akorn, Inc.	HYDASE	hyaluronidase	Injection	021716	10/25/2005		2030-04-09
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	01/16/1978		2030-04-09
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2030-04-09