Abstract: An interferon-beta (IFN?) analog peptide including a plurality of amino acid substitutions in an amino acid sequence of IFN? as set forth in SEQ ID No. 4. The IFN? analog peptide may include a plurality of amino acid substitution in the amino acid sequence of IFN? in at least one position of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 18, 19, 20, 21, 22, 23, 24, and combinations thereof, numbered in accordance with SEQ ID No. 4.
Type:
Grant
Filed:
October 4, 2018
Date of Patent:
August 11, 2020
Inventors:
Mansour Poorebrahim, Matin Asghari, Mohammad Hossein Nasr-Esfahani, Nima Sanadgol, Mohammad Foad Abazari, Maryam Nouri Aleagha, Hassan Askari, Solmaz Sadeghi
Abstract: In certain embodiments, the invention provides a method of purifying a protein of interest from a mixture which comprises the protein of interest and one or more contaminants, comprising: a) subjecting the mixture to a first chromatography step; b) recovering the protein of interest in an elution solution; c) adding caprylic acid to the elution solution to form a contaminant precipitate; d) removing the contaminant precipitate from the elution solution; and e) subjecting the post-precipitated elution solution to a second chromatography column, thereby purifying the protein of interest.
Abstract: The present invention provides, among other aspects, methods for the manufacture of plasma-derived immunoglobulin G compositions highly enriched for anti-brain disease related protein antibodies (e.g., anti-A?, anti-RAGE, and anti-?-synuclein antibodies). Advantageously, the methods provided do not affect the manufacturing processes or capabilities for producing plasma-derived IgG therapeutics. Plasma-derived IgG compositions that are highly enriched for anti-brain disease related protein antibodies (e.g., anti-A?, anti-RAGE, and anti-?-synuclein antibodies), as also provided here. Methods for the treatment of brain diseases and disorders by administration of plasma-derived IgG compositions highly enriched for anti-brain disease related protein antibodies (e.g., anti-A?, anti-RAGE, and anti-?-synuclein antibodies), are also provided.
Type:
Grant
Filed:
December 20, 2016
Date of Patent:
August 11, 2020
Assignees:
Baxalta Incorporated, Baxalta GmbH
Inventors:
Lucia Gnauer, Harald Arno Butterweck, Theresa Bauer, Alfred Weber, Wolfgang Teschner, Hans-Peter Schwarz
Abstract: Antibodies or antigen-binding fragments thereof are engineered to bind Transforming Growth Factor-? (TGF?). TGF?-isoform selective antibodies or antigen-binding fragments thereof may selectively bind human TGF?1, compared to human TGF?2 and human TGF?3, or may selectively bind human TGF?3, compared to human TGF?1 and human TGF?2. The design of the antibodies or antigen-binding fragments thereof is facilitated by a co-crystal structure of a recombinant Fab fragment of GC1008 bound to TGF?2 and by another co-crystal structure of the scFv version of GC1008 bound to TGF?1.
Type:
Grant
Filed:
August 7, 2017
Date of Patent:
August 4, 2020
Assignee:
GENZYME CORPORATION
Inventors:
Ronnie Wei, Aaron Moulin, Magali Mathieu, Clark Pan, Sunghae Park, Huawei Qiu
Abstract: Provided is an affinity chromatography carrier that maintains high immunoglobulin-binding capacity and high alkali resistance. An immunoglobulin-binding protein including at least one modified immunoglobulin-binding domain, the modified immunoglobulin-binding domain being a polypeptide consisting of an amino acid sequence of an immunoglobulin-binding domain selected from the group consisting of the B domain, Z domain, C domain, and variants thereof of Staphylococcus aureus protein A, in which at least one amino acid residue is inserted between positions corresponding to the 3-position and position 4 of the amino acid sequence of the B domain, Z domain or C domain.
Type:
Grant
Filed:
March 24, 2016
Date of Patent:
July 28, 2020
Assignees:
JSR CORPORATION, JSR LIFE SCIENCES CORPORATION
Abstract: For the removal of high molecular weight compounds from recombinantly produced polypeptides generally chromatographic methods are employed. It has been found that underivatized controlled pore glass (uCPG) selectively binds high molecular weight compounds present in a solution. The purified polypeptide can be recovered e.g. from the flow through of a chromatography column containing uCPG as chromatography material. It has been found that this effect is pronounced at a pH value of about 4 to 6 in buffered solutions. With approximately 100 m2 to 150 m2 uCPG surface per g of polypeptide almost 80% to 95% of the high molecular weight compounds are removed with a yield of 80% to 90% of polypeptide.
Type:
Grant
Filed:
April 13, 2017
Date of Patent:
July 28, 2020
Assignee:
Hoffman-La Roche Inc.
Inventors:
Stefan Hepbildikler, Wolfgang Kuhne, Eva Rosenberg, Gerhard Winter
Abstract: The present inventors discovered that neural invasion is suppressed by inhibiting IL-6 in a model for neural invasion of pancreatic cancer, and completed the present invention. The present inventors also demonstrated that: an IL-6 receptor is expressed in cells of human pancreatic cancer cell lines; and IL-6 enhances the chemotactic and migratory activities and intracellular signaling of pancreatic cancer cells; and thus pancreatic cancer can be treated by inhibiting IL-6. Furthermore, the present inventors found that neural invasion of human pancreatic cancer can be suppressed, from the results of administering IL-6 inhibitors to neural invasion model mice.
Type:
Grant
Filed:
June 5, 2009
Date of Patent:
July 21, 2020
Assignees:
National Cancer Center, Chugai Seiyako Kabushiki Kaisha
Abstract: Eculizumab, a humanized monoclonal antibody against C5 that inhibits terminal complement activation, showed activity in a preliminary 12-week open-label trial in a small cohort of patients with paroxysmal nocturnal hemoglobinuria (PNH). The present study examined whether chronic eculizumab therapy could reduce intravascular hemolysis, stabilize hemoglobin levels, reduce transfusion requirements, and improve quality of life in a double-blind, randomized, placebo-controlled, multi-center global Phase III trial. It has been found that eculizumab stabilized hemoglobin levels, decreased the need for transfusions, and improved quality of life in PNH patients via reduced intravascular hemolysis. Chronic eculizumab treatment appears to be a safe and effective therapy for PNH.
Type:
Grant
Filed:
February 28, 2020
Date of Patent:
July 7, 2020
Assignee:
Alexion Pharmaceuticals, Inc.
Inventors:
Leonard Bell, Russell P. Rother, Mark J. Evans
Abstract: Combinations of different chromatography modalities with particularly refined conditions significantly reduce acid charge variants in a preparation of monoclonal antibodies. The process for reducing acid charge variants utilizes a combination of anion exchange and hydrophobic interaction chromatography, followed by cation exchange chromatography polishing, whereby the levels of acidic or basic charge species of the monoclonal antibodies may be modulated to a desired level.
Type:
Grant
Filed:
January 21, 2016
Date of Patent:
June 30, 2020
Assignee:
Outlook Therapeutics, Inc.
Inventors:
Chris Yonan, Christine Caroselli, Wiphusanee Dendamrongvit, Scott Gangloff
Abstract: In certain embodiments, the invention provides a method of purifying a protein of interest from a mixture which comprises the protein of interest and one or more contaminants, said method comprising: a) subjecting the mixture to a first chromatography matrix, wherein the protein of interest binds to the first chromatography matrix; b) contacting the first chromatography matrix with a first wash solution which has a pH of at least 9.0, and does not comprise arginine or an arginine derivative; and c) eluting the protein of interest from the first chromatography matrix into an elution solution.
Abstract: Described herein is secretory IgA isolated from the intestinal luminal fluid and intestinal mucosal of animals such as pigs and cows. Also included are methods of isolating secretory IgA. The secretory IgA is useful in food compositions such as animal and human food compositions as well as pharmaceutical compositions to increase growth rate, improve feed efficiency, reduce gastrointestinal inflammation, reduce a risk of gastrointestinal infection in the animal, or a combination thereof.
Abstract: Disclosed herein is a T-helper cell (“TH-GM” cell) that is regulated by IL-7/STAT5 and which secrete GM-CSF/IL-3. Also disclosed are methods and compositions for modulating TH-GM function for the treatment of, e.g., inflammatory disorders. Diagnostic and prognostic methods for specifically identifying TH-GM-mediated inflammatory disorders (e.g., rheumatoid arthritis), as distinct from and/or in addition to non-TH-GM-mediated (e.g., TNF-?-mediated) inflammatory disorders, are also provided.
Type:
Grant
Filed:
September 25, 2015
Date of Patent:
June 23, 2020
Assignee:
NATIONAL UNIVERSITY OF SINGAPORE
Inventors:
Fu Xin-Yuan, Wanqiang Sheng, Yongliang Zhang, Fan Yang
Abstract: A wash buffer comprising greater than 0 mM and less than about 500 mM arginine, greater than 0 mM and less than about 250 mM guanidine, greater than 0 mM and less than about 250 mM sodium chloride, and greater than 0 mM and less than about 50 mM of an anionic surfactant, or greater than 0% and less than about 0.25% w/v of a non-ionic surfactant. When used during affinity chromatography purification of a protein of interest, such as an antibody, the wash buffer significantly reduces the level of host cell proteins from the preparation. Following affinity chromatography with the wash buffer, the protein of interest may be further purified using membrane chromatography.
Type:
Grant
Filed:
July 25, 2017
Date of Patent:
June 23, 2020
Assignee:
Cehpalon, Inc.
Inventors:
Lu Wang, Tianyi Zhou, Zhaoqing Zhang, Mi Jin
Abstract: A method for purifying a protein comprising an antibody, antibody fragment, or immunoglobulin single variable domain, from a solution containing at least one contaminant by superantigen chromatography comprising: a) adsorbing the protein to the superantigen immobilized on a solid support; b) removing the at least one contaminant by contacting the immobilized superantigen containing the adsorbed protein with a first wash buffer comprising an aliphatic carboxylate; and c) eluting the protein from the superantigen immobilized on the solid support.
Abstract: Provided herein are de novo binding domain containing polypeptides (DBDpp) that specifically bind a target of interest. Nucleic acids encoding the DBDpp, and vectors and host cells containing the nucleic acids are also provided. Libraries of DBDpp, methods of producing and screening such libraries and the DBDpp identified from such libraries and screens are also encompassed. Methods of making and using the DBDpp are additionally provided. Such uses include, without limitation, affinity purification, and diagnostic and therapeutic applications.
Type:
Grant
Filed:
April 4, 2016
Date of Patent:
May 26, 2020
Assignees:
Subdomain LLC, Arcellx, Inc.
Inventors:
David William Lafleur, David M. Hilbert
Abstract: Disclosed are methods and compositions for selectively targeting sites of traumatic brain injury (TBI). A brain injury-specific 4-amino acid peptide (sequence CAQK), identified by in vivo phage display screening in mice with acute brain injury, shows selective binding to mouse and human brain injury lesions, and when systemically injected, specifically homes to sites of injury in penetrating and non-penetrating (controlled cortical impact) brain injury models. Also disclosed are methods and compositions for delivering therapeutic compounds to such sites. CAQK-coated nanoparticles containing silencing oligonucleotides provide an alternative to local delivery of therapeutics, which is invasive and can add complications to the injury.
Type:
Grant
Filed:
September 2, 2016
Date of Patent:
May 19, 2020
Assignee:
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
Inventors:
Erkki Ruoslahti, Aman Mann, Pablo Scodeller, Sazid Hussain
Abstract: The present inventors discovered that additional aggregation of low-pI antibody can be suppressed by removing formed antibody aggregates after a certain period of time following Protein A column purification, acidic treatment, and neutralization. Furthermore, the present inventors found that efficient impurities removal for a low-pI antibody can be accomplished by using an anion exchange resin in the Bind/Elute mode and then a hydrophobic interaction chromatography or multimodal chromatography resin, compared with conventional methods.
Abstract: Provided herein are de novo binding domain containing polypeptides (DBDpp) that specifically bind a target of interest. Nucleic acids encoding the DBDpp, and vectors and host cells containing the nucleic acids are also provided. Libraries of DBDpp, methods of producing and screening such libraries and the DBDpp identified from such libraries and screens are also encompassed. Methods of making and using the DBDpp are additionally provided. Such uses include, without limitation, affinity purification, and diagnostic and therapeutic applications.
Type:
Grant
Filed:
April 4, 2016
Date of Patent:
May 12, 2020
Assignees:
Subdomain LLC, Arcellx, Inc.
Inventors:
David William Lafleur, David M. Hilbert
Abstract: Disclosed herein are methods that have been developed to control the formation of disulfide bonds between polypeptides of a multimeric protein produced by a bioprocess. Also disclosed are protein solution parameters that allow for controlling the formation of disulfide bonds. In one example, the methods disclosed herein can be used to control the proportion of half antibody molecules in an antibody solution.
Type:
Grant
Filed:
March 25, 2015
Date of Patent:
May 12, 2020
Assignee:
GENZYME CORPORATION
Inventors:
Kevin P. Brower, Chris Hwang, Rao Koduri, Konstantin B. Konstantinov, Veena Warikoo, Marcella Yu, Jin Yin