Beta Globulins, E.g., Transferrin, Etc. Patents (Class 530/394)
-
Publication number: 20080274958Abstract: The present invention provides sequon polypeptides with an amino acid sequence including one or more exogenous O-linked glycosylation sequence of the invention. In addition, the present invention provides methods of making polypeptide conjugates as well as methods of using such conjugates and their pharmaceutical compositions. The invention further provides libraries of sequon polypeptides, wherein each member of such library includes at least one exogenous O-linked glycosylation sequence of the invention. Also provided are methods of making and using such libraries.Type: ApplicationFiled: July 23, 2007Publication date: November 6, 2008Applicant: Neose Technologies, Inc.Inventor: Shawn DeFrees
-
Publication number: 20080255040Abstract: The present invention provides sequon polypeptides with an amino acid sequence including one or more exogenous O-linked glycosylation sequence of the invention. In addition, the present invention provides methods of making polypeptide conjugates as well as methods of using such conjugates and their pharmaceutical compositions. The invention further provides libraries of sequon polypeptides, wherein each member of such library includes at least one exogenous O-linked glycosylation sequence of the invention. Also provided are methods of making and using such libraries.Type: ApplicationFiled: July 23, 2007Publication date: October 16, 2008Applicant: Neose Technologies, Inc.Inventor: Shawn DeFrees
-
Publication number: 20080248959Abstract: The present invention provides sequon polypeptides with an amino acid sequence including one or more exogenous O-linked glycosylation sequence of the invention. In addition, the present invention provides methods of making polypeptide conjugates as well as methods of using such conjugates and their pharmaceutical compositions. The invention further provides libraries of sequon polypeptides, wherein each member of such library includes at least one exogenous O-linked glycosylation sequence of the invention. Also provided are methods of making and using such libraries.Type: ApplicationFiled: July 23, 2007Publication date: October 9, 2008Applicant: Neose Technologies, Inc.Inventor: Shawn DeFrees
-
Publication number: 20080242607Abstract: The present invention provides sequon polypeptides with an amino acid sequence including one or more exogenous O-linked glycosylation sequence of the invention. In addition, the present invention provides methods of making polypeptide conjugates as well as methods of using such conjugates and their pharmaceutical compositions. The invention further provides libraries of sequon polypeptides, wherein each member of such library includes at least one exogenous O-linked glycosylation sequence of the invention. Also provided are methods of making and using such libraries.Type: ApplicationFiled: July 23, 2007Publication date: October 2, 2008Applicant: Neose Technologies, Inc.Inventor: Shawn DeFrees
-
Publication number: 20080206260Abstract: Chimeric fusion proteins comprising Neisseria transferrin binding proteins (Tbps) from, for example, N. gonorrhoeae and/or N. meningitidis are provided. The fusion proteins elicit an antibody response in the mucosa of the urogenital and/or oropharynx tract, as well as in the serum. The resulting serum antibodies are cross-bactericidal against heterologous bacterial strains. The chimeric proteins also comprise a mucosal adjuvant such as a toxin subunit, e.g. the B subunit of cholera toxin or of Escherichia coli heat labile toxin II. Methods of inhibiting the growth of Neisseria species on mucosal surfaces of a mammal by either administering the fusion proteins of the invention, or antibodies directed to the fusion proteins of the invention, to the mammal.Type: ApplicationFiled: December 21, 2007Publication date: August 28, 2008Inventors: Cynthia Nau Cornelissen, Gregory Price, Michael Russell, Terry Connell
-
Publication number: 20080154022Abstract: Compositions and methods for increasing the receptor mediated transport of basic fibroblast growth factor (bFGF) across the blood brain barrier (BBB). The bFGF is conjugated to a BBB targeting agent using either avidin-biotin technology or genetic engineering. The bFGF conjugate was found to cross the BBB at substantially increased rates while still retaining biological activity. In addition, uptake of the bFGF conjugate by non-brain tissue and organs was limited. The bFGF conjugate may be injected intravenously to provide neuroprotection in patients suffering from cerebral stroke.Type: ApplicationFiled: June 1, 2007Publication date: June 26, 2008Applicant: The Regents of the University of CaliforniaInventors: Dafang Wu, William M. Pardridge
-
Patent number: 7285646Abstract: The present invention relates to an ultrapure human transferrin, and to methods for manufacturing the ultrapure transferrin. The transferrin may be holo-, apo- or at any desired degree of iron saturation. The invention further relates to the use of ultrapure transferrin as the protein moiety of conjugates, and to pharmaceutical compositions comprising ultra transferrin alone as well as in the form of a conjugate.Type: GrantFiled: October 13, 2004Date of Patent: October 23, 2007Assignee: Kamada Ltd.Inventor: Shabtai Bauer
-
Patent number: 7176278Abstract: The present invention discloses fusion proteins comprising transferrin, lactoferrin or melanotransferrin fused to glucagon-like peptide 1 (GLP-1). In one embodiment of the invention, the fusion protein displays increased serum half-life as compared to a GLP-1 peptide in an unfused state. The invention includes a pharmaceutical composition comprising the GLP-1 fusion protein of the invention and a carrier. The fusion protein of the invention can be administered to a subject for treatment of diseases or conditions treatable by GLP-1, including, but not limited to, diabetes, obesity, congestive heart failure and inflammatory bowel syndrome.Type: GrantFiled: March 4, 2003Date of Patent: February 13, 2007Assignee: BioRexis Technology, Inc.Inventor: Christopher P. Prior
-
Patent number: 7101842Abstract: Targeting agents such as transferrin and transcobalamin can be conjugated with anti-protozoan drugs for the treatment of protozoan infections. Any suitable anti-protozoan drug can be used, preferably the drug is selected from the group consisting of apoptosis inducing compounds, cytotoxic antibiotics, alkalating agents, plant toxins, and bacterial mutant toxins. The targeting agent is preferably coupled to the antiprotozoan drug by means of glutaraldehyde.Type: GrantFiled: May 16, 2002Date of Patent: September 5, 2006Assignee: Faulk Pharmaceuticals, Inc.Inventor: W. Page Faulk
-
Patent number: 7053185Abstract: A method for producing an oligomeric form of ?-lactalbumin which is in the molten globule-like state is described. The method suitably comprises exposing a source of ?-lactalbumin in which the ?-lactalbumin is preferably in the molten globule-like state, to an ion exchange medium which has been pre-treated with casein or an active component thereof, such as oleic acid, and recovering ?-lactalbumin in an oligomeric form therefrom. Pre-treatment of the ion exchange medium, particularly with casein derived from human milk, has been found to significantly improve yields of the oligomeric form of ?-lactalbumin and means that it can be readily isolated from readily available sources such as bovine ?-lactalbumin. This form of ?-lactalbumin is useful therapeutically, in particular as an antibacterial agent and also as an anti-cancer therapeutic.Type: GrantFiled: November 23, 1998Date of Patent: May 30, 2006Assignee: HAMLET Pharma ABInventors: Catharina Svanborg, Per Anders Hakansson, Malin Wilhelmina Svensson
-
Patent number: 7030088Abstract: The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the secreted peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the secreted peptides, and methods of identifying modulators of the secreted peptides.Type: GrantFiled: September 30, 2004Date of Patent: April 18, 2006Assignee: Applera CorporationInventors: Toni Ceccardi, Emanuel Langit, Min Zhong, Istvan Ladunga
-
Patent number: 6881828Abstract: A hybrid fusion protein comprising a first antigenic amino acid sequence fused to a second amino acid sequence substantially homologous to B2M or a fragment thereof.Type: GrantFiled: April 8, 1994Date of Patent: April 19, 2005Assignee: Isis Innovations LimitedInventors: Richard Mark Edwards, Michael George Hunter
-
Patent number: 6825037Abstract: Recombinant transferrin, non-glycosylated recombinant transferrin, transferrin half-molecules and mutant transferrins having altered metal-binding or other properties are described. The recombinant transferrin molecules are expressed in functional form by stable eukaryotic cell lines such as baby hamster kidney cells transformed with an expression vector encoding the recombinant molecule. The recombinant transferrins can be used in metal chelation therapy to bind and clear excess toxic metals in patients suffering from metal overloads or as tissue culture medium supplements or replacements.Type: GrantFiled: November 15, 1999Date of Patent: November 30, 2004Assignees: University of Vermont, University of British ColumbiaInventors: Walter D. Funk, Ross T.A. MacGillivray, Anne B. Mason, Robert C. Woodworth
-
Patent number: 6328966Abstract: The invention pertains to eutrophic drug composition containing transferrins, particularly human transferrins. This composition allows the toxic effects of cytotoxic drugs such as cyclosporin when used at high dosages or over a prolonged period of time to be alleviated or suppressed.Type: GrantFiled: July 23, 1997Date of Patent: December 11, 2001Assignee: I.S.I.S.P.A.Inventor: Walter Pierpaoli
-
Patent number: 6326473Abstract: The present invention relates to pharmaceutical compositions of transferrin and to the manufacture of such preparations. The present invention concerns specifically a pharmaceutical composition of apotransferrin, the iron-free form of transferrin, wherein the composition has at least 90% of the theoretical iron binding capacity of iron-free transferrin, contains less than 3% transferrin dimers and no detectable transferrin polymers or aggregates, and has an iron-saturation of less than 5%. The pharmaceutical apotransferrin composition of this invention effectively binds non-transferrin-bound-iron to a harmless form when administered as an intravenous injection or infusion to patients. The pharmaceutical composition of this invention does not contain viruses, denatured forms of transferrin or other harmful components.Type: GrantFiled: December 30, 1998Date of Patent: December 4, 2001Assignee: Suomen Punainen Risti VeripalveluInventors: Jaakko Parkkinen, Leni von Bonsdorff-Lindeberg
-
Patent number: 6319498Abstract: Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural &bgr; amyloid peptides (&bgr;-AP). In a preferred embodiment, the &bgr; amyloid modulator compounds of the invention are comprised of an A&bgr; aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural &bgr; amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural &bgr;-AP aggregation when the natural &bgr;-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.Type: GrantFiled: March 14, 1996Date of Patent: November 20, 2001Assignee: Praecis Pharmaceuticals IncorporatedInventors: Mark A. Findeis, Howard Benjamin, Marc B. Garnick, Malcolm L. Gefter, Arvind Hundal, Laura Kasman, Gary Musso, Ethan R. Signer, James Wakefield, Michael J. Reed
-
Patent number: 6251860Abstract: The present invention relates to pharmaceutical compositions of transferrin and to the manufacture of such preparations. The present invention concerns specifically a pharmaceutical composition of apotransferrin, the iron-free form of transferrin, wherein the composition has at least 90% of the theoretical iron binding capacity of iron-free transferrin, contains less than 3% transferrin dimers and no detectable transferrin polymers or aggregates, and has an iron-saturation of less than 5%. The pharmaceutical apotransferrin composition of this invention effectively binds non-transferrin-bound-iron to a harmless form when administered as an intravenous injection or infusion to patients. The pharmaceutical composition of this invention does not contain viruses, denatured forms of transferrin or other harmful components.Type: GrantFiled: April 27, 1999Date of Patent: June 26, 2001Assignee: Suomen Punainen Risti VeripalveluInventors: Jaakko Parkkinen, Leni von Bonsdorff-Lindeberg
-
Patent number: 6153408Abstract: An altered MHC class I determinant comprises .alpha..sub.1, .alpha..sub.2, .alpha..sub.3, .beta..sub.2 -microglobulin (.beta..sub.2 m) polypeptide domains encoded by a mammalian MHC class I locus in which the .alpha..sub.3 domain is covalently linked to the .beta..sub.2 M domain. An altered MHC class II determinant comprises .alpha..sub.1, .alpha..sub.2, .beta..sub.1, and .beta..sub.2 polypeptide domains encoded by a mammalian MHC class II locus, in which the domains are covalently linked to form a polypeptide comprising the .beta..sub.2 -.alpha..sub.2 -.alpha..sub.1 -.beta..sub.1 domains in sequence. The altered MHC class I and class II determinants can be associated with an antigen to elicit an immune response. The invention can be used in the immunization or treatment of diseases such as AIDS, multiple sclerosis, lupus erythematosus, toxic shock or snake bite.Type: GrantFiled: January 9, 1995Date of Patent: November 28, 2000Assignee: Institut Pasteur and Institut National de la Sante et de la Recherche MedicaleInventors: Jean-Pierre Abastado, Estelle Mottez, Philippe Kourilsky, Armanda Casrouge, David Ojcius, Yu-Chun Lone
-
Patent number: 6096870Abstract: The present invention is related to the separation of whey proteins, particularly the sequential separation of whey proteins into separate fractions through the use of chromatography. The present invention further provides methods and compositions for the sequential separation of whey proteins, as well as their use in various products. The present invention also provides methods and compositions for the cleaning of chromatography resins used in the separation of whey proteins.Type: GrantFiled: May 4, 1998Date of Patent: August 1, 2000Assignee: Sepragen CorporationInventors: Zahid Mozaffar, Salah H. Ahmed, Vinit Saxena, Quirinus Ronnie Miranda
-
Patent number: 5986063Abstract: A method is provided for isolating the proteins, .beta.-lactoglobulin and .alpha.-lactalbumin, from whey with a single cation exchanger, and using different pH values for eluting the proteins as separate fractions without using salt elution. A whey protein solution is adjusted to a pH of less than about 4.5. The solution is contacted with a cation exchanger to obtain a bound fraction containing .alpha.-lactalbumin and .beta.-lactoglobulin. The bound fraction is adjusted to a pH of about 4.0 to 6.0 and a .beta.-lactoglobulin fraction is eluted at this pH in the absence of sodium chloride. The pH of an remaining bound fraction is adjusted to about 6.5 or greater and an .alpha.-lactalbumin fraction is eluted. The method is advantageously conducted at elevated temperatures ranging from 35.degree. C. to 50.degree. C.Type: GrantFiled: July 31, 1998Date of Patent: November 16, 1999Assignee: Wisconsin Alumni Research FoundationInventor: Mark R. Etzel
-
Patent number: 5986067Abstract: Recombinant transferrin, non-glycosylated recombinant transferrin, transferrin half-molecules and mutant transferrins having altered metal-binding or other properties are described. The recombinant transferrin molecules are expressed in functional form by stable eukaryotic cell lines such as baby hamster kidney cells transformed with an expression vector encoding the recombinant molecule. The recombinant transferrins can be used in metal chelation therapy to bind and clear excess toxic metals in patients suffering from metal overloads or as tissue culture medium supplements or replacements.Type: GrantFiled: December 28, 1993Date of Patent: November 16, 1999Assignees: The University of Vermont and State Agricultural College, The University of British ColumbiaInventors: Walter D. Funk, Ross T. A. MacGillivray, Anne B. Mason, Robert C. Woodworth
-
Patent number: 5985275Abstract: A composition is provided which comprises a protein or peptide containing lysines, wherein at least one of the lysines and/or the N-terminal amino group of the protein or peptide, such as casein, .beta.-lactoglobulin, powdered milk or whey, is modified by contact with an aromatic acid anhydride compound, such as trimellitic anhydride, trimellitic anhydride chloride or 3-hydroxyphthalic anhydride. Additionally a composition is provided wherein a protein or peptide containing arginines is modified by an arginine modifying agent containing at least one carboxyl group, such as p-carboxyphenylglyoxal. The compositions are capable of binding to CD4 cell receptors, such as the HIV-1 or HIV-2 binding site on CD4 cell receptors. The compositions are thus useful for the prevention of HIV-1 or HIV-2 infection, especially by local administration.Type: GrantFiled: September 29, 1995Date of Patent: November 16, 1999Assignee: New York Blood CenterInventors: Alexander Robert Neurath, Asim Kumar Debnath, Shibo Jiang
-
Patent number: 5914312Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described. Also, clearing agents, anti-ligand-targeting moiety conjugates, target cell retention enhancing moieties and additional methods are discussed.Type: GrantFiled: August 26, 1994Date of Patent: June 22, 1999Assignee: NeoRx CorporationInventors: Donald B. Axworthy, Alan R. Fritzberg, James A. Sanderson
-
Patent number: 5833988Abstract: The present invention pertains to a method for delivering a neuropharmaceutical or diagnostic agent across the blood brain barrier to the brain of a host. The method comprises administering to the host a therapeutically effective amount of an antibody-neuropharmaceutical or diagnostic agent conjugate wherein the antibody is reactive with a transferrin receptor. Other aspects of this invention include a delivery system comprising an antibody reactive with a transferrin receptor linked to a neuropharmaceutical or diagnostic agent and methods for treating hosts afflicted with a disease associated with a neurological disorder.Type: GrantFiled: April 18, 1996Date of Patent: November 10, 1998Assignee: Alkermes, Inc.Inventor: Phillip M. Friden
-
Patent number: 5827737Abstract: The present invention relates to a rational, elegant means of producing, loading and using Class I molecules to specifically activate CD8 cells in vitro, and their therapeutic applications in the treatment of a variety of conditions, including cancer, tumors or neoplasias, as well as viral, retroviral, autoimmune, and autoimmune-type diseases. The present invention also relates to vectors, cell lines, recombinant DNA molecules encoding human .beta.2 microglobulin or Class I MHC molecules in soluble and insoluble form, and methods of producing same.Type: GrantFiled: June 24, 1996Date of Patent: October 27, 1998Assignee: The Scripps Research InstituteInventors: Per A. Peterson, Michael Jackson, Pierre Langlade-Demoyen
-
Patent number: 5817765Abstract: Virus inactivating chemicals and/or detergents in an aqueous composition containing a water-soluble plasma protein are reduced by selecting a suitable combination of temperature and concentration above 0.5M of salt with a high salting out effect according to the Hofmeister series, thereby forming vesicles containing the virus inactivating chemical and/or detergent. These vesicles are removed from the aqueous phase, e.g. by phase separation or filtration, and the protein thereafter isolated from the aqueous phase. The water-soluble plasma protein can be e.g. antithrombin III, transferrin or albumin. When the aqueous phase comprises e.g. a salt of citrate or sulphate in a concentration above 1M at room temperature, the reduction of virus inactivating chemical or detergent can be as high as 2000 times or more, giving a final concentration below 5 ppm.Type: GrantFiled: October 30, 1995Date of Patent: October 6, 1998Assignee: Pharmacia & Upjohn AktiebolagInventors: Sven Isaksson, Stefan Winge
-
Patent number: 5756680Abstract: A method is disclosed for the sequential separation of whey proteins using radial-flow chromatography. Different buffer systems adjusted to suitable pH and ionic strength are utilized in the separation process. The method separates at least five different proteins from whey. Infant feeding formulas, and other food formulations are also disclosed incorporating therein in different proportions various proteins separated from the whey.Type: GrantFiled: July 16, 1996Date of Patent: May 26, 1998Assignee: Sepragen CorporationInventors: Salah H. Ahmed, Vinit Saxena, Zahid Mozaffar, Quirinus R. Miranda
-
Patent number: 5744586Abstract: Method for obtaining highly purified transferrin from a partially purified plasma fraction containing transferrin in which the starting fraction is concentrated. Its ionic strength is reduced and then transferrin is adsorbed onto a chromatographic column. Following elution, the transferrin can be further processed through to packaging in final containers. The final purified transferrin product is sterile, at least 95% pure and is substantially free of enveloped and non-enveloped viruses.Type: GrantFiled: June 26, 1996Date of Patent: April 28, 1998Assignee: Alpha Therapeutic CorporationInventors: John M. Rolf, Akimasa Ohmizu, Shawn D. Latham, Prabir Bhattacharya
-
Patent number: 5728383Abstract: Potent and specific immunotoxins are prepared by conjugation of moieties binding to receptors on the surface of tumor cells to a mutant diphtheria toxin having A-chain translocation activity, but lacking membrane-binding activity. The immunotoxins are used to treat primary tumors of neurologic origin, metastatic tumors of small cell lung carcinoma or breast carcinoma origin, leptomeningeal leukemia and leptomeningeal carcinomatosis. The preferred route of administration of the immunotoxin is to a compartment of the body containing cerebrospinal fluid.Type: GrantFiled: June 13, 1994Date of Patent: March 17, 1998Assignee: The United States of America as represented by the Secretary of the Department of Health and Human ServicesInventors: Virginia Johnson, Richard J. Youle
-
Patent number: 5679780Abstract: High quality protein products are obtained from whey by subjecting whey to cross flow filtration in microfilter. The whey and retentate are brought to circulate in a circulation path on one side of the membrane area of the microfilter, while whey which has passed through the membrane area (permeate) is circulating in a second path on the other side of the membrane area in such a way that the pressure drop through the whole membrane area is kept constant and below 0.8 bar. With this technique, there is obtained a fractionation of milk serum protein such that denatured milk serum protein and fat are retained in the retentate and undenatured milk serum protein passes through the membrane into the permeate. With a subsequent treatment there is obtained a whey protein product which is rich is .alpha.-lactalbumin and .beta.-lactoglobulin and has a low fat content.Type: GrantFiled: January 3, 1995Date of Patent: October 21, 1997Assignee: Tetra Laval Holdings & Finance S.A.Inventors: John Jensen, Peter Henrik Larsen
-
Patent number: 5648469Abstract: Monoclonal antibodies have been produced which specifically bind to epitopes found in the cytoplasmic domain of the transferrin receptor (TR). The antibodies are useful for isolating sequences in a sample which contain TR cytoplasmic domain.Type: GrantFiled: May 19, 1995Date of Patent: July 15, 1997Assignee: The Salk Institute for Biological StudiesInventors: Ian S. Trowbridge, Suhaila N. White
-
Patent number: 5606086Abstract: Heat resistant carbonate- and/or hydrogencarbonate-iron-Lf complexes in which one molecule of lactoferrin is bound with 15 molecules or over of iron via carbonic acid and/or hydrogencarbonic acid.Process for the production of above mentioned complexes prepared by adjusting pH.ltoreq.7 by adding alkali salts of carbonic acid and/or hydrogencarbonic acid to an aqueous solution containing an iron salt exhibiting pH.ltoreq.4 when dissolved in water and lactoferrins, or adding an iron salt and lactoferrin solution to carbonic acid and/or hydrogencarbonic acid solution, or adding the iron salt or its solution to a solution containing carbonic acid and/or hydrogencarbonic acid and lactoferrins.The resultant lactoferrin complexes are highly heat resistant and useful as raw materials of foods, medicines, feeds, cosmetics and so forth.Type: GrantFiled: April 24, 1995Date of Patent: February 25, 1997Assignee: Snow Brand Milk Products Co., Ltd.Inventors: Shunichi Dosako, Toshio Sakurai, Naomichi Kobayashi
-
Patent number: 5576299Abstract: The protein lactoferrin can be used both for treating and/or preventing of portunistic infections frequently complicating Immunodeficiency Virus positive animals including human beings. The protein greatly improves the quality of life in such immunodeficiency virus infected animals. The dosage of the protein is usually 0.1-100 mg/kg daily, and preferably 0.5-50 mg/kg.Type: GrantFiled: March 2, 1993Date of Patent: November 19, 1996Assignee: Immuno Japan, Inc.Inventors: Kunio Ando, Junichi Kishimoto
-
Patent number: 5498600Abstract: Dimeric proteins having substantially the same biological activity as PDGF are disclosed. More specifically, the proteins may have two polypeptide chains, one of the chains being a mosaic of amino acid sequences substantially identical to portions of the A- or B-chains of PDGF, the second of the chains being substantially homologous to either the A-chain or the B-chain of PDGF, the proteins being chemotactic or mitogenic for fibroblasts. Alternatively, each of the two polypeptide chains may be a mosaic of amino acid sequences as described above. Therapeutic compositions containing these proteins and methods for enhancing the wound-healing process in warm-blooded animals are also disclosed.Type: GrantFiled: October 7, 1994Date of Patent: March 12, 1996Assignee: ZymoGenetics, Inc.Inventors: Mark J. Murray, James D. Kelly
-
Patent number: 5442043Abstract: The present invention provides a conjugate capable of passing the blood-brain barrier comprising a bioactive peptide or protein incapable of passing the blood-brain barrier and a carrier peptide which exhibits substantially no bioactivity and which is capable of passing the blood-brain barrier. The conjugate makes it possible to allow a bioactive peptide or protein incapable of passing the blood-brain barrier to easily pass the blood-brain barrier for uniform transport to the brain without any side effect of the carrier peptide.Type: GrantFiled: November 29, 1993Date of Patent: August 15, 1995Assignee: Takeda Chemical Industries, Ltd.Inventors: Makoto Fukuta, Satoshi Iinuma, Hiroaki Okada
-
Patent number: 5393737Abstract: A novel composition of matter comprising a ligand-carbohydrate-cytotoxic drug conjugate is produced by the steps of (1) reacting a carbohydrate with a ligand, (2) reacting the product of step (1) with a cytotoxic drug, and (3) stabilizing the product of step (2) by reduction. The composition is used for treating a neoplastic disease by a process of administering a non-toxic, effective amount of a ligand-carbohydrate-cytotoxic drug conjugate to a human being or animal in need of such a treatment.Type: GrantFiled: August 20, 1992Date of Patent: February 28, 1995Assignee: Health Research, Inc.Inventors: George L. Mayers, Jafar Razeq, Mahmoud M. Abu-Hadid
-
Patent number: 5352447Abstract: A potent and specific immunotoxin is prepared by coupling a binding-site inactivated diphtheria toxin (CRM 107) to a new binding moiety consisting of transferrin or a monoclonal antibody against the human transferrin receptor. These immunotoxins are tumor specific and lack the nonspecific toxicity produced by the binding activity of the native toxin. The immunotoxin is useful in treating primary brain tumors, metastatic tumors to the brain, CSF-borne tumors, leptomeningeal leukemia and leptomeningeal carcinomatosis.Type: GrantFiled: August 10, 1992Date of Patent: October 4, 1994Assignee: The United States of America as represented by the Secretary of the Department of Health and Human ServicesInventors: Virginia Johnson, Richard J. Youle
-
Patent number: 5292869Abstract: The present invention relates to a method for isolating and purifying transferrin and lactoferrin receptor proteins from bacterial pathogens by affinity chromatography and to the preparation of vaccine antigens containing the purified receptor proteins.Type: GrantFiled: April 11, 1990Date of Patent: March 8, 1994Assignee: The Board of Governors of the UniversityInventor: Anthony B. Schryvers
-
Patent number: 5256412Abstract: The invention relates to an anti-HIV agent comprising as an effective component a plasma protein of which the polarity of the amino group of the amino acid residue constituting the plasma protein is chemically modified into a negative moiety by a carboxylic acid, for example, by maleic anhydride or succinic anhydride. Plasma proteins modified with dicarboxylic anhydride, which are the effective components of the anti-HIV agent of this invention, inhibit the formation of large cells in mixed culturing of HIV infected cells and non-infected cells as well as the direct infection of helper T cells with HIV.Type: GrantFiled: August 17, 1992Date of Patent: October 26, 1993Assignee: Meiji Milk Products Co., Ltd.Inventors: Hajime Tsunoo, Masao Takami, Kenji Mizumoto
-
Patent number: 5252715Abstract: A process for the preparation of an iron-free, pasteurized human transferrin is described and entails human transferrin being pasteurized in the presence of a complexing agent in solution, and the complexing agent being removed with the bound iron.This transferrin can be used as pharmaceutical or growth factor.Type: GrantFiled: December 11, 1991Date of Patent: October 12, 1993Assignee: Behringwerke AktiengesellschaftInventor: Heinz Haupt
-
Patent number: 5208323Abstract: The present invention relates to antitumor compounds of the formula I: ##STR1## wherein M is selected from the group consisting of an hydrogen atom, a peptide residue, and a protein residue linked to the carbon atom via the amino residue of .epsilon.-lysine present therein which can be an antibody used to target the anti-tumor agent to the malignant cells, and R can be an antitumor agent such as daunorubicin, doxorubicin, or an epirublicin derivative.Type: GrantFiled: January 13, 1992Date of Patent: May 4, 1993Assignee: Universite LavalInventors: Michel Page, Denis Thibeault
-
Patent number: 5164486Abstract: The invention relates to an anti-HIV agent comprising as an effective component a plasma protein of which the polarity of the amino group of the amino acid residue constituting the plasma protein is chemically modified into a negative moiety by a carboxylic acid, for example, by maleic anhydride or succinic anhydride.Plasma proteins modified with dicarboxylic anhydride, which are the effective components of the anti-HIV agent of this invention, inhibit the formation of large cells in mixed culturing of HIV infected cells and non-infected cells as well as the direct infection of helper T cells with HIV. They are very safe compounds and are expected to be applicable to the treatment of HIV infected patients.Type: GrantFiled: September 10, 1990Date of Patent: November 17, 1992Assignee: Meiji Milk Products Co., Ltd.Inventors: Hajime Tsunoo, Masao Takami, Kenji Mizumoto
-
Patent number: 5138034Abstract: A method of fractionating plasma protein which comprises treating a plasma protein-containing material in the following sequence of steps, provided that steps (ii) through (v) may be performed in an optional order: (i) freeze-thaw treatment, (ii) treatment at 5 to 10% ethanol concentration, (iii) treatment with an anion exchanger, (iv) affinity chromatography with immobilized lysine, (v) affinity chromatography with immobilized heparin, (vi) treatment at 18 to 30% ethanol concentration, (vii) treatment at 35 to 45% ethanol concentration.Type: GrantFiled: June 14, 1990Date of Patent: August 11, 1992Assignee: The Green Cross CorporationInventors: Yahiro Uemura, Kazuo Takechi, Kenji Tanaka
-
Patent number: 5136026Abstract: A process for removing toxins from solutions of proteins, in which an aqueous solution of a protein which contains a buffer substance, a chelating agent and a detergent is subjected to an ion exchange chromatography, is described.Type: GrantFiled: April 9, 1991Date of Patent: August 4, 1992Assignee: Behringwerke AktiengesellschaftInventors: Jurgen Romisch, Norbert Heimburger
-
Patent number: 5122368Abstract: The invention relates to anthracycline conjugates comprising at least one anthracycline molecule linked to a molecule that is reactive with a cell population to be eliminated such as antibody, bombesin, EGF and transferrin. Each anthracycline molecule, having a keto group at the C-13 position, is conjugated to the antibody via a linker arm and is bound to that linker arm via an acid-sensitive acylhydrazone bond at the 13-keto position of the anthracycline. The linker additionally contains a disulfide or thioether linkage as part of the antibody or ligand attachment to the immunoconjugate. The novel anthracycline acylhydrazone derivatives are useful in the preparation of the conjugates of this invention. The acid-sensitive hydrazone bond of the conjugates of this invention allows the release of free anthracycline from the conjugates in the acidic external or internal environment of the target cell.Type: GrantFiled: May 17, 1989Date of Patent: June 16, 1992Assignee: Bristol-Myers Squibb CompanyInventors: Robert S. Greenfield, Gary R. Braslawsky, Lee J. Olech, Takushi Kaneko, Peter A, Kiener
-
Patent number: 5108987Abstract: Conjugates of transferrin or ceruloplasmin with anti-tumour agents. Such conjugates are useful in the treatment of tumours. Suitable anti-tumour agents include adriamycin, daunomycin, methotrexate, vincristin, 6-mercaptopurine, cytosine arabinoside and cyclophosphamide. Transferrin or ceruloplasmin in preferably coupled to the anti-tumour agent by means of glutaraldehyde.Type: GrantFiled: July 31, 1989Date of Patent: April 28, 1992Inventor: Ward P. Faulk
-
Patent number: 5051185Abstract: An adsorbent for .beta..sub.2 -microglobulin is disclosed, which comprises a water-insoluble carrier having supported thereon, as a ligand, at least one electrolyte selected from the group consisting of a polyamino acid, a polysaccharide, a synthetic high polymer, collagen having an isoelectric point of 9.5 or more, and gelatin having an isoelectric point of 6.5 or more, wherein said electrolyte has a molecular weight not less than 1,000 and an X value of more than 2.0, wherein X is a relationship regarding the skeleton structure of said electrolyte and is the sum of A and B, wherein A represents (the number of carbon atoms of the skeleton structure)-(the number of hydrophilic groups)/(the number of hydrophilic groups); and B represents .vertline.(the number of cationic groups)-(the number of anionic groups).vertline./(the number of hydrophilic groups). The adsorbent exhibits adsorptivity for .beta..sub.2 -microglobulin at high efficiency and high selectivity.Type: GrantFiled: April 19, 1990Date of Patent: September 24, 1991Assignees: Asahi Kasei Kogyo K.K., Asahi Medical Co., Ltd.Inventors: Hiroyuki Watanabe, Tadashi Yokoyama, Naokuni Yamawaki
-
Patent number: 5051371Abstract: Substantially pure modified .beta..sub.2 -microglobulin (m.beta..sub.2 m) of the formula I ##STR1## wherein R.sub.1 is 24-amino acid residue, with the sequence Ile-Gln-Arg-Thr-Pro-Lys-Ile-Gln-Val-Tyr-Ser-Arg-His-Pro-Ala-Glu-Asn-Gly-Ly s-Ser-Asn-Phe-Leu-Asn, R.sub.2 is a 30-amino acid residue with the sequence Tyr-Val-Ser-Gly-Phe-His-Pro-Ser-Asp-Ile-Glu-Val-Asp-Leu-Leu-Lys-Asn-Gly-Gl u-Arg-Ile-Gly-Lys-Val-Glu-His-Ser-Asp-Leu-Ser, R.sub.3 is a 20-amino acid residue with the sequence Trp-Ser-Phe-Tyr-Leu-Leu-Tyr-Tyr-Glu-Phe-Thr-Pro-Thr-Glu-Lys-Asp-Glu-Tyr-Al a, R.sub.4 is a 19-amino acid residue with the sequence Arg-Val-Asn-His-Val-Thr-Leu-Ser-Gln-Pro-Lys-Ile-Val-Lys-Trp-Asp-Arg-Asp-Me t, X is Phe, Phe-Ser, or Phe-Ser-Lys, and Y is Asp, Lys-Asp, or Ser-Lys-Asp is disclosed. The presence of the protein in body fluids is a diagnostic and/or prognostic marker for the development of a variety of disorders such as different types of cancer and diseases involving the immune system. Also disclosed are specific anti-m.Type: GrantFiled: January 15, 1987Date of Patent: September 24, 1991Assignee: Noyo Nordisk A/SInventors: Mogens H. Nissen, Jesper Zeuthen, Flemming S. Larsen, Lars Thim, Mogens Christensen
-
Patent number: 5041537Abstract: To provide a simple method of preparing biologically active transferrin that can be employed on an industrial scale and that will result in extremely pure and natural transferrin containing no viruses and appropriate for both in-vitro and in-vivo applications, the .gamma.-globulins are precipitated from the fraction containing the transferrin, the precipitant is removed from the residual liquid by ultrafiltration or gel filtration, the liquid is adjusted to a prescribed ionic concentration and protein concentration and (a) treated with .beta.-propiolactone and the solution is subjected to ultraviolet radiation or (b) treated with specific detergents and subjected to ion-exchange chromatography, and the transferrin is concentrated and filtered sterile.Type: GrantFiled: September 27, 1988Date of Patent: August 20, 1991Assignee: Biotest Pharma GmbHInventors: Ulf Bethke, Norbert Kothe, Dieter Rudnick, Wolfgang Moller, Michael Kloft
-
Patent number: 5000935Abstract: Conjugates of transferrin with a radioactive isotope of iodine are utilized to treat cancer in animals.Type: GrantFiled: November 17, 1989Date of Patent: March 19, 1991Inventor: Ward P. Faulk