Conjugated Via A Specifically-identified Linking Group, Coupling Agent, Or Conjugation Agent Patents (Class 530/391.9)
  • Patent number: 9993568
    Abstract: Provided are methods of use of compounds comprising a self-immolative group, which compounds may include a protein (for example, an oligopeptide, a polypeptide, an antibody, or the like) having substrate-specificity for a target and an active agent (for example, a drug, a toxin, a ligand, a detection probe, or the like) having a specific function or activity.
    Type: Grant
    Filed: May 27, 2015
    Date of Patent: June 12, 2018
    Assignee: LegoChem Biosciences, Inc.
    Inventors: Yong Zu Kim, Tae Kyo Park, Sung Ho Woo, Sun Young Kim, Jong Un Cho, Doo Hwan Jung, Ji Young Min, Hyang Sook Lee, Yun Hee Park, Jeong Hee Ryu, Kyu Man Oh, Yeong Soo Oh, Jeiwook Chae, Ho Young Song, Chul-Woong Chung, Jeon Yang
  • Patent number: 9849191
    Abstract: A polymeric scaffold useful for conjugating with a protein based recognition-molecule (PBRM) to form a PBRM-polymer-drug conjugate is described herein. The scaffold includes one or more terminal maleimido groups. Also disclosed is a PBRM-polymer-drug conjugate prepared from the scaffold. Compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions are also described.
    Type: Grant
    Filed: October 10, 2014
    Date of Patent: December 26, 2017
    Assignee: Mersana Therapeutics, Inc.
    Inventors: Aleksandr V. Yurkovetskiy, Mao Yin, Timothy B. Lowinger, Joshua D. Thomas, Cheri A. Stevenson, Venu R. Gurijala
  • Patent number: 9428543
    Abstract: The invention provides a one-step process for preparing a cell-binding agent cytotoxic agent conjugate comprising contacting a cell-binding agent with a cytotoxic agent to form a first mixture comprising the cell-binding agent and the cytotoxic agent and contacting the first mixture comprising the cell-binding agent and the cytotoxic agent with a bifunctional crosslinking reagent, which provides a linker, in a solution having a pH of about 4 to about 9 to provide a second mixture comprising the cell-binding agent cytotoxic agent conjugate, wherein the cell-binding agent is chemically coupled through the linker to the cytotoxic agent, free cytotoxic agent, and reaction by-products. The second mixture is then optionally subjected to purification to provide a purified cell-binding agent cytotoxic agent conjugate.
    Type: Grant
    Filed: June 24, 2014
    Date of Patent: August 30, 2016
    Assignee: ImmunoGen, Inc.
    Inventors: Xinfang Li, Jared M. Worful
  • Patent number: 9376500
    Abstract: This invention describes a method of conjugating a cell binding agent such as an antibody with an effector group (e.g., a cytotoxic agent) or a reporter group (e.g., a radionuclide), whereby the reporter or effector group is first reacted with a bifunctional linker and the mixture is then used without purification for the conjugation reaction with the cell binding agent. The method described in this invention is advantageous for preparation of stably-linked conjugates of cell binding agents, such as antibodies with effector or reporter groups. This conjugation method provides in high yields conjugates of high purity and homogeneity that are without inter-chain cross-linking and inactivated linker residues.
    Type: Grant
    Filed: December 3, 2013
    Date of Patent: June 28, 2016
    Assignee: ImmunoGen, Inc.
    Inventors: Brenda A. Kellogg, Rajeeva Singh, Ravi V. J. Chari
  • Patent number: 9341635
    Abstract: A reactive mass label for labelling a biological molecule for detection by mass spectrometry, which label comprises a reactive functionality for labelling thiol groups or carbonyl groups. Also provided is a reactive mass label for labelling a biological molecule for detection by mass spectrometry, wherein the mass label comprises the following structure: X-L-M-S—Re wherein X is a mass marker moiety, L is a cleavable linker, M is a mass normalization moiety, S is a mass series modifying group comprising the following group: wherein J is C?O, K is NH, and n is 2 or J and K are both CH2 and n is 1, and wherein m is at least 1; and Re is a reactive functionality for attaching the mass label to a biological molecule.
    Type: Grant
    Filed: September 8, 2010
    Date of Patent: May 17, 2016
    Assignee: ELECTROPHORETICS LIMITED
    Inventors: Christian Baumann, Stefan Kienle, Karsten Kuhn, Harald Legner
  • Patent number: 9226973
    Abstract: The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to EGP-1 (TROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUC5ac and the immunoconjugate may be administered at a dosage of between 4 mg/kg and 24 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.
    Type: Grant
    Filed: March 11, 2014
    Date of Patent: January 5, 2016
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, David M. Goldenberg
  • Patent number: 9221759
    Abstract: The invention relates to novel luminescent compositions of matter containing a fluorophore, synthetic methods for making the compositions, macromolecular conjugates of the compositions, and the use of the compositions in various methods of detection. The invention also provides kits containing the compositions and their conjugates for use in the methods of detection.
    Type: Grant
    Filed: January 13, 2011
    Date of Patent: December 29, 2015
    Assignees: Rutgers, the State University of New Jersey, New Jersey Institute of Technology
    Inventors: Arkady Mustaev, Maxim Kozlov, Salvatore Marras, Lev Krasnoperov, Laura Wirpsza, Shyamala Pillai
  • Patent number: 9216276
    Abstract: This invention provides methods and systems uniquely capable of enhancing medicant delivery and/or effectiveness through the use of energy to predictably disrupt membranes and mechanically and thermally modulate cells and tissues. In exemplary embodiments, the methods and systems disclosed herein are capable of modulating multiple layers of tissue. In an exemplary embodiment, the energy is acoustic energy (e.g., ultrasound). In other exemplary embodiments, the energy is photon based energy (e.g., IPL, LED, laser, white light, etc.), or other energy forms, such radio frequency electric currents, or various combinations of acoustic energy, electromagnetic energy and other energy forms or energy absorbers such as cooling. Medicants can be first introduced to the region of interest by diffusion, circulation, and/or injection. An exemplary system for enhancing medicant delivery and/or effectiveness comprises a control system, a probe, and a display or indicator system.
    Type: Grant
    Filed: May 7, 2008
    Date of Patent: December 22, 2015
    Assignee: Guided Therapy Systems, LLC
    Inventors: Michael H. Slayton, Peter G. Barthe, Inder Raj S. Makin
  • Patent number: 9173958
    Abstract: Compositions and methods are provided in embodiments directed to maintaining a desired concentration range of one or more drugs in a subject, and in particular embodiments to maintaining a desired drug concentration in a body compartment in a subject, based on the surprising discovery that antibodies persist in solution in body compartments such that antibody-antigen equilibrium principles can counteract drug clearance mechanisms. One or more antibodies are selected that have a dissociation constant KD that is similar to the desired drug concentration, wherein KD is independent of the affinity of the drug for a specific drug target (receptor) in the subject.
    Type: Grant
    Filed: September 13, 2005
    Date of Patent: November 3, 2015
    Assignee: Arrowsmith Technologies Corporation
    Inventors: Jefferson Foote, Carol E. O'Hear
  • Patent number: 9175083
    Abstract: Novel antigen-binding polypeptides (ABP) and uses thereof are provided.
    Type: Grant
    Filed: October 16, 2007
    Date of Patent: November 3, 2015
    Assignee: AMBRX, INC.
    Inventors: Ho Sung Cho, Thomas O. Daniel, Troy E. Wilson, Thomas P. Cujec, Feng Tian, Anna-Maria A. Hays, Bruce E. Kimmel, Lillian Ho
  • Publication number: 20150141624
    Abstract: This invention relates to anti-CD70 antibodies and antibody drug conjugates comprising at least one non-naturally-encoded amino acid. Disclosed herein are ?CD70 antibodies with one or more non-naturally encoded amino acids and further disclosed are antibody drug conjugates wherein the ?CD70 antibodies of the invention are conjugated to one or more toxins. Further disclosed are methods for using such non-natural amino acid antibody drug conjugates, including therapeutic, diagnostic, and other biotechnology uses.
    Type: Application
    Filed: June 19, 2013
    Publication date: May 21, 2015
    Applicant: AMBRX, INC.
    Inventors: Richard S. Barnett, Nick Knudsen, Ying Sun, Sandra Biroc, Timothy Buss, Tsotne Javahishvili, Damien Bresson, Shailaja Srinagesh, Amha Hewet, Jason K. Pinkstaff
  • Publication number: 20150141625
    Abstract: The present invention provides IRM conjugates that includes an IRM moiety and a second active moiety covalently linked to the IRM moiety in which the covalent link does not depend on UV irradiation.
    Type: Application
    Filed: January 20, 2015
    Publication date: May 21, 2015
    Inventors: Doris Stoermer, George W. Griesgraber, James D. Mendoza, Jason D. Bonk
  • Patent number: 9028833
    Abstract: The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to EGP-1 (TROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUC5ac and the immunoconjugate may be administered at a dosage of between 4 mg/kg and 24 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.
    Type: Grant
    Filed: July 23, 2013
    Date of Patent: May 12, 2015
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, David M. Goldenberg
  • Publication number: 20150125473
    Abstract: The present invention concerns a process for the preparation of an antibody conjugate comprising the step of reacting an engineered antibody having a single inter-heavy chain disulfide bond with a conjugating reagent that forms a bridge between the two cysteine residues derived from the disulfide bond.
    Type: Application
    Filed: June 19, 2013
    Publication date: May 7, 2015
    Inventors: John Burt, Antony Godwin, George Badescu
  • Publication number: 20150125474
    Abstract: A polymeric scaffold useful for conjugating with a protein based recognition-molecule (PBRM) to form a PBRM-polymer-drug conjugate is described herein. The scaffold includes one or more terminal maleimido groups. Also disclosed is a PBRM-polymer-drug conjugate prepared from the scaffold. Compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions are also described.
    Type: Application
    Filed: October 10, 2014
    Publication date: May 7, 2015
    Inventors: Roger A. Smith, Nitin K. Damle, Aleksandr V. Yurkovetskiy, Mao Yin, Timothy B. Lowinger, Joshua D. Thomas, Cheri A. Stevenson, Venu R. Gurijala
  • Publication number: 20150125472
    Abstract: The present invention provides for anti-EFNA4 antibody-drug conjugates and methods for preparing and using the same.
    Type: Application
    Filed: October 28, 2014
    Publication date: May 7, 2015
    Applicants: STEM CENTRX, INC., PFIZER, INC.
    Inventors: Marc Isaac DAMELIN, Kiran Manohar KHANDKE, Puja SAPRA, Alexander John BANKOVICH, Scott J. DYLLA
  • Publication number: 20150125386
    Abstract: The present invention concerns compositions and methods of use of a humanized Class III anti-CEA antibody, comprising the heavy and light amino acid sequences SEQ ID NO:1 and SEQ ID NO:2. The antibody is effective to treat CEACAM5-expressing tumors, either alone or in combination with one or more therapeutic agents. Drug conjugated Class III anti-CEA antibodies, such as SN-38 or P2PDox immunoconjugates, are particularly efficacious. Surprisingly, the antibody-drug conjugates (ADCs) exhibit high anti-cancer efficacy, while exhibiting low levels of systemic toxicity that are readily treated with standard amelioration techniques. Antibodies and/or immunoconjugates comprising the amino acid sequences SEQ ID NO:1 and SEQ ID NO:2 are surprisingly efficacious for therapy of solid tumors, even when the tumor has proven resistant to standard anti-cancer therapies.
    Type: Application
    Filed: October 16, 2014
    Publication date: May 7, 2015
    Inventors: Hans J. Hansen, David M. Goldenberg
  • Publication number: 20150110815
    Abstract: The present invention relates to a drug conjugate comprising a cytotoxic drug conjugated to a c-Met specific human antibody. More specifically, the present invention relates to: a drug conjugate comprising a cytotoxic drug conjugated to a c-Met specific human antibody; a pharmaceutical composition for cancer treatment comprising the drug conjugate; and a cancer treatment method comprising a step in which the drug conjugate or pharmaceutical composition is administered to an individual.
    Type: Application
    Filed: November 28, 2012
    Publication date: April 23, 2015
    Applicant: Korea Research Institute of Bioscience and Biotechnology
    Inventors: Young Woo Park, Ki Won Jo, Sun Jeong Jo, Soon Sil Hyun, Jae Eun Park, Seok Ho Yoo, Myeoung Hee Jang, Hye Nan Kim, Chan Woong Park
  • Publication number: 20150105540
    Abstract: There is disclosed an improved ADC (antibody drug conjugate) type composition having at least two different drug payloads conjugated to a single targeting protein. More specifically, the present disclosure attaches a first drug conjugate to a dual Cysteine residue on a targeting protein and a second drug conjugate with a different drug to a Lys residue on the targeting protein.
    Type: Application
    Filed: October 15, 2014
    Publication date: April 16, 2015
    Applicant: Sorrento Therapeutics Inc.
    Inventors: Zhenwei Miao, Gang Chen, Tong Zhu, Alisher B. Khasanov, Yufeng Hong, Hong D. Zhang, Alexander Chucholowski
  • Publication number: 20150105539
    Abstract: In one aspect, an active agent-conjugate, methods of preparing the active agent-conjugate, and uses thereof is provided.
    Type: Application
    Filed: May 14, 2013
    Publication date: April 16, 2015
    Applicant: Concortis Biosystems, Corp., a wholly owned Subsidiary of Sorrento Therapeutics, Inc.
    Inventors: Zhenwei Miao, Yufeng Hong, Tong Zhu, Alexander Wilhelm Chucholowski
  • Publication number: 20150104468
    Abstract: The present disclosure provides methods of site-specific labeling of antibodies, using proteins having 4?-phosphopantetheinyl transferase activity that catalyze post-translational modification of peptide sequences (“peptide tags”) incorporated into one or more specific sites of an antibody of interest. Enzymatic labeling enables quantitative and irreversible covalent modification of a specific serine residue within the peptide tags incorporated into the antibody, and thus creates desirable antibody conjugates.
    Type: Application
    Filed: May 31, 2013
    Publication date: April 16, 2015
    Applicant: IRM LLC
    Inventors: Bernhard Hubert Geierstanger, Jan Grunewald, Badry Bursulaya
  • Publication number: 20150104469
    Abstract: The invention provides carriers that enhance the absorption, half-life or bioavailability of therapeutic compounds. The carriers comprise targeting groups that bind the Vitamin D Binding protein (DBP), conjugation groups for coupling the targeting groups to the therapeutic compounds, and optionally scaffolding moieties.
    Type: Application
    Filed: March 14, 2013
    Publication date: April 16, 2015
    Applicant: Extend Biosciences, Inc.
    Inventors: Tarik Soliman, Laura M. Hales, Howard P. Sard, Mukkanti Amere
  • Publication number: 20150105541
    Abstract: The invention provides protein-active agent conjugates having an amino acid motif that can be recognized by an isoprenoid transferase. The invention also provides compositions containing the conjugates. The invention further provides methods for using the conjugates to deliver the active agent to a target cell, as well as methods for using the conjugates to treat a subject in need thereof (e.g.
    Type: Application
    Filed: October 17, 2014
    Publication date: April 16, 2015
    Inventors: Yongzu Kim, Taekyo Park, Sungho Woo, Hyangsook Lee, Sunyoung Kim, Jongun Cho, Doohwan Jung, Youngun Kim, Hyunjin Kwon, Kyuman Oh, Yunseo Chung, Yun-Hee Park
  • Patent number: 9005625
    Abstract: The present invention provides conjugates formed between toxins and sugars and toxins and peptides, such as antibodies. In an exemplary embodiment, a toxin-sugar construct is conjugated to an antibody through an intact glycosyl linking group.
    Type: Grant
    Filed: July 26, 2004
    Date of Patent: April 14, 2015
    Assignee: Novo Nordisk A/S
    Inventors: Shawn DeFrees, Zhi-Guang Wang
  • Patent number: 9005910
    Abstract: The purpose is to produce, with high reproducibility, a complex of labeled probes and a carrier, said complex being to be used for detecting and measuring a target substance to be measured with high sensitivity and high stability. The means for accomplishing the purpose is that a label is bound to a probe-water soluble carrier conjugate using specific binding of an avidin compound such as avidin, streptavidin, etc. to biotin, and the binding of the avidin compound to the probe is performed before the binding to the carrier. Namely, after conjugating the avidin compound to a substance which is capable of binding to the target substance, the conjugate is bound to a high-molecule water-soluble carrier to produce a complex of the avidinized probes and the water-soluble carrier. Then the complex of the avidinized probes and the water-soluble carrier is mixed with a biotinylated label.
    Type: Grant
    Filed: April 13, 2011
    Date of Patent: April 14, 2015
    Assignees: Eiken Kagaku Kabushiki Kaisha, Advanced Life Science Institute, Inc.
    Inventors: Yoshiyuki Ohiro, Susumu Takayasu
  • Publication number: 20150098900
    Abstract: The invention provides anti-FcRH5 antibodies and immunoconjugates and methods of using the same.
    Type: Application
    Filed: June 24, 2014
    Publication date: April 9, 2015
    Inventors: Allen J. Ebens, Meredith C. Hazen, Jo-Anne Hongo, Jennifer W. Johnston, Teemu T. Junttila, Ji Li, Andrew G. Polson
  • Publication number: 20150099865
    Abstract: A method is disclosed for preparing hydrazides from hydrazine and an acyl chloride which comprises the steps of (a) preparing a stirred substantially uniform slurry comprising hydrazine and an inert solvent at low temperature; and (b) adding an acyl chloride continuously to said slurry. The method avoids or limits production of undesired bis-hydrazide by-products. The method is used to prepare 3-methyl-3-mercaptobutanoic acid hydrazide, a molecule used to link calicheamicin to a monoclonal antibody.
    Type: Application
    Filed: October 2, 2014
    Publication date: April 9, 2015
    Applicant: WYETH LLC
    Inventors: George Anello CHIARELLO, Ayman SAHLI
  • Publication number: 20150094456
    Abstract: The invention relates to therapeutic conjugates with the ability to target various antigens. The conjugates contain a targeting antibody or antigen binding fragment thereof and an anthracycline chemotherapeutic drug. The targeting antibody and the chemotherapeutic drug are linked via a linker comprising a hydrazide moiety.
    Type: Application
    Filed: October 17, 2014
    Publication date: April 2, 2015
    Inventors: Gary L. Griffiths, Hans J. Hansen, Zhengxing Qu, David M. Goldenberg
  • Publication number: 20150093397
    Abstract: Methods to improve the success of cancer therapies that target CD37 are provided. Kits comprising reagent useful in the methods are further provided.
    Type: Application
    Filed: March 29, 2013
    Publication date: April 2, 2015
    Inventor: Christina N. Carrigan
  • Patent number: 8992932
    Abstract: The present application relates to new binder-drug conjugates (ADCs) of N,N-dialkylauristatins that are directed against the target C4.4a, to active metabolites of these ADCs, to processes for preparing these ADCs, to the use of these ADCs for treating and/or preventing illnesses, and also to the use of these ADCs for producing medicaments for treating and/or preventing illnesses, more particularly hyperproliferative and/or angiogenic diseases such as, for example, cancer diseases. Such treatments may be practiced as a monotherapy or else in combination with other medicaments or further therapeutic measures.
    Type: Grant
    Filed: October 20, 2012
    Date of Patent: March 31, 2015
    Assignee: Seattle Genetics, Inc.
    Inventors: Hans-Georg Lerchen, Lars Linden, Sherif El Sheikh, Jörg Willuda, Charlotte Christine Kopitz, Joachim Schuhmacher, Simone Greven, Christoph Mahlert, Beatrix Stelte-Ludwig, Sven Golfier, Rudolf Beier, Iring Heisler, Axel Harrenga, Karl-Heinz Thierauch, Sandra Bruder, Heike Petrul, Hannah Jöriβen, Sandra Borkowski
  • Patent number: 8993524
    Abstract: The present invention is based on the seminal discovery that targeted immunomodulatory antibodies and fusion proteins can counter act or reverse immune tolerance of cancer cells. Cancer cells are able to escape elimination by chemotherapeutic agents or tumor-targeted antibodies via specific immunosuppressive mechanisms in the tumor microenvironment and such ability of cancer cells is recognized as immune tolerance. Such immune suppressive mechanisms include immunosuppressive cytokines (for example, Transforming growth factor beta (TGF-?) and regulatory T cells and/or immunosuppressive myeloid dendritic cells (DCs). By counteracting tumor-induced immune tolerance, the present invention provides effective compositions and methods for cancer treatment, optional in combination with another existing cancer treatment.
    Type: Grant
    Filed: March 4, 2011
    Date of Patent: March 31, 2015
    Assignee: The Johns Hopkins University
    Inventors: Atul Bedi, Rajani Ravi
  • Publication number: 20150087814
    Abstract: The present invention provides for recombinant Endo-S mutants that exhibit reduced hydrolysis activity and increased transglycosylation activity for the synthesis of glycoproteins wherein a desired sialylated oxazoline or synthetic oligosaccharide oxazoline is added to a core fucosylated or nonfucosylated GlcNAc-protein acceptor. Such recombinant Endo-S mutants are useful for efficient glycosylation remodeling of IgGl-Fc domain to provide different antibody glycoforms carrying structurally well-defined Fc N-glycans.
    Type: Application
    Filed: February 11, 2013
    Publication date: March 26, 2015
    Inventors: Lai-Xi Wang, Wei Huang
  • Publication number: 20150086576
    Abstract: In some aspects, polypeptides comprising single domain antibodies and methods of identifying single domain antibodies are provided. In some embodiments polypeptides comprising a single domain antibody and a sortase recognition sequence, are provided. In some aspects, products and methods of use in modulating the immune system, e.g., modulating an immune response, are provided.
    Type: Application
    Filed: April 15, 2013
    Publication date: March 26, 2015
    Inventors: Hidde Ploegh, Maximilian Popp, Juanjo Cragnolini
  • Patent number: 8987424
    Abstract: Cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate are disclosed are all embodiments of the invention. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CA6 glycotope. The present invention is also directed to humanized or resurfaced versions of DS6, an anti-CA6 murine monoclonal antibody, and epitope-binding fragments thereof.
    Type: Grant
    Filed: April 13, 2008
    Date of Patent: March 24, 2015
    Assignee: ImmunoGen, Inc.
    Inventors: Gillian Payne, Philip Chun, Daniel J. Tavares
  • Patent number: 8987425
    Abstract: The invention provides a fusion protein comprising (a) a first protein comprising a polypeptide which specifically binds to Annexin A1 and (b) a second protein comprising a polypeptide which induces a cytotoxic activity of a cytotoxic lymphocyte, pharmaceutical compositions comprising the fusion protein, and methods of treating or preventing cancer by administering the pharmaceutical compositions.
    Type: Grant
    Filed: July 25, 2012
    Date of Patent: March 24, 2015
    Assignee: Samsung Electronics Co., Ltd.
    Inventor: Jae-il Lee
  • Publication number: 20150079114
    Abstract: Ligand Drug Conjugates are provided having a DRS binding moiety attached via linking groups andor spacers to a therapeutic agent that are effective in treatment of various cancers. In some embodiments, the Ligand Drug Conjugate has the formula: L-(LU-D)p, where L is a Ligand unit, LU is a Linker unit and D is a Drug unit (or cytotoxic agent). The subscript p is an integer of from 1 to 20. Accordingly, the Ligand Drug Conjugates comprise a Ligand unit covalently linked to at least one Drug unit. The Drug units can be covalently linked directly or via a Linker unit (-LU-). The Ligand unit is a DR5 binding agent, such as an anti-DRS antibody.
    Type: Application
    Filed: April 23, 2013
    Publication date: March 19, 2015
    Inventors: Toshiaki Ohtsuka, Kimihisa Ichikawa, Ayumi Yada
  • Publication number: 20150080559
    Abstract: Disclosed herein are non-natural amino acids and dolastatin analogs that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The dolastatin analogs can include a wide range of possible functionalities, but typically have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid dolastatin analogs and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology uses.
    Type: Application
    Filed: May 24, 2012
    Publication date: March 19, 2015
    Applicant: AMBRX, INC.
    Inventors: Zhenwei Miao, Kyle Atkinson, Sandra Biroc, Timothy Buss, Melissa Neal, Vadim Kraynov, Robin Mardsen, Jason Pinkstaff, Lillian Skidmore, Ying Sun, Agnieszka Szydlik, Ianina Valenta
  • Patent number: 8980265
    Abstract: Subject matter of the invention are antibody-cytokine fusion proteins having proapoptotic and immune modulating properties, but wherein the cytokine moiety a priori has a bioactivity which is very low or restricted to certain receptor subtypes. These reagent exert their full biological activity via the corresponding cytokine receptor(s) only after antibody-mediated binding of the fusion protein to a specific cell membrane-expressed target molecule. By suitable choice of the antibody specificity, the cytokine activity is directed to the tissue, e.g. tumor tissue, to be treated, and a therapeutic agent can be produced being specifically designed/optimized for the respective indication/tumor entity.
    Type: Grant
    Filed: March 14, 2003
    Date of Patent: March 17, 2015
    Assignee: BioNTech AG
    Inventors: Klaus Pfizenmaier, Harald Wajant, Dieter Moosmayer, Thomas Wuest
  • Patent number: 8980824
    Abstract: Tubulysin compounds of the formula (I) where R1, R2, R3a, R3b, R4, R5, W, and n are as defined herein, are anti-mitotic agents that can be used in the treatment of cancer, especially when conjugated to a targeting moiety.
    Type: Grant
    Filed: February 11, 2014
    Date of Patent: March 17, 2015
    Assignee: Bristol-Myers Squibb Company
    Inventors: Qiang Cong, Heng Cheng, Sanjeev Gangwar
  • Publication number: 20150071949
    Abstract: New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the ?-carbon atom bearing the sulfur atom are disclosed. Also disclosed are methods for the synthesis of these new maytansinoids and methods for the linkage of these new maytansinoids to cell-binding agents. The maytansinoid-cell-binding agent conjugates are useful as therapeutic agents, which are delivered specifically to target cells and are cytotoxic. These conjugates display vastly improved therapeutic efficacy in animal tumor models compared to the previously described agents.
    Type: Application
    Filed: August 14, 2014
    Publication date: March 12, 2015
    Inventors: Ravi V.J. Chari, Wayne C. Widdison
  • Publication number: 20150071948
    Abstract: The present invention relates to Fc variants with optimized Fc ligand binding properties, methods for their generation, Fc polypeptides comprising Fc variants with optimized Fc ligand binding properties, and methods for using same.
    Type: Application
    Filed: March 13, 2014
    Publication date: March 12, 2015
    Inventors: Gregory Alan Lazar, Bassil Dahiyat, Wei Dang, John Desjarlais, Sher Bahadur Karki, Omid Vafa, Robert Hayes, Jost Vielmetter
  • Publication number: 20150071923
    Abstract: Provided herein are modified anti-EGFR antibodies and nucleic acid molecules encoding modified anti-EGFR antibodies. Also provided are methods of treatment and uses using modified anti-EGFR antibodies.
    Type: Application
    Filed: September 12, 2014
    Publication date: March 12, 2015
    Inventors: Ge Wei, Gregory I. Frost, H. Michael Shepard, Christopher D. Thanos
  • Publication number: 20150071950
    Abstract: Disclosed is a conjugate in which a c-Met targeting compound and a bioactive material are chemically conjugated with each other, and methods of use thereof.
    Type: Application
    Filed: September 12, 2014
    Publication date: March 12, 2015
    Inventors: Su Young Chae, Sunghyun Kim, Eun Ko, Yun Ju Jeong, Jae Hyun Choi
  • Publication number: 20150056223
    Abstract: The present invention relates to a pharmaceutical composition for the prevention and treatment of non-alcoholic fatty liver disease (NAFLD), including a conjugate prepared by covalently linking an insulinotropic peptide, a non-peptidyl polymer and an immunoglobulin Fc region. The composition of the present invention maintains the in-vivo activity of the peptide at a relatively high level, and remarkably increases the blood half-life, thereby preventing triglyceride accumulation which is a typical feature of non-alcoholic fatty liver disease. Ultimately, it can be desirably employed for the prevention and treatment of non-alcoholic fatty liver disease.
    Type: Application
    Filed: March 8, 2013
    Publication date: February 26, 2015
    Applicant: HANMI SCIENCE CO., LTD
    Inventors: Se Young Lim, Sung Hee Park, Ryoung Ae Shin, In Young Choi, Se Chang Kwon
  • Publication number: 20150056222
    Abstract: The present invention provides antibodies that bind to prolactin receptor (PRLR) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human PRLR with high affinity. In certain embodiments, the invention includes antibodies that bind PRLR and block prolactin-mediated cell signaling. In other embodiments, the invention includes antibodies that bind PRLR but do not block prolactin-mediated cell signaling. According to certain embodiments, the invention includes antibodies that bind to the first fibronectin-like type III domain of the extracellular domain of PRLR. The antibodies of the invention may be fully human antibodies. The invention includes anti-PRLR antibodies conjugated to a cytotoxic agent, radionuclide, or other moiety detrimental to cell growth or proliferation. The antibodies of the invention are useful for the treatment of various cancers as well as other PRLR-related disorders.
    Type: Application
    Filed: October 31, 2014
    Publication date: February 26, 2015
    Inventors: Nicholas J. PAPADOPOULOS, Gavin THURSTON, Jessica R. KIRSHNER, Marcus P. KELLY, Thomas NITTOLI, Frank J. DELFINO, William C. OLSON, Yashu LIU
  • Publication number: 20150051380
    Abstract: The present invention relates to conjugates of therapeutically useful anthracyclines with carriers such as polyclonal and monoclonal antibodies, proteins or peptides of natural or synthetic origin; methods for their preparation, pharmaceutical composition containing them and use thereof in treating certain mammalian tumors.
    Type: Application
    Filed: October 30, 2014
    Publication date: February 19, 2015
    Applicant: Genentech, Inc.
    Inventors: Italo Beria, Michele Caruso, John A. Flygare, Vittoria Lupi, Rita Perego, Paul Polakis, Andrew Polson, Matteo Salsa, Susan D. Spencer, Barbara Valsasina, Robert L. Cohen
  • Publication number: 20150044216
    Abstract: Provided are bispecific antibodies having a full-size antibody portion with two light chains and two heavy chains, wherein the two heavy chains each is fused to a single-chain variable fragment (scFv) portion. In certain embodiments, the full-size antibody has specificity to EGFR and the scFv has specificity to VEGF.
    Type: Application
    Filed: August 5, 2014
    Publication date: February 12, 2015
    Inventors: Xiaoyun Wu, Shengfeng Li, Chenchao Xu
  • Publication number: 20150037360
    Abstract: The present invention relates to a linker for forming conjugates of a protein or peptide with a therapeutically active agent and which comprise a thiomaleamic acid moiety that is susceptible to cleavage under the pH conditions prevalent in the lysosome.
    Type: Application
    Filed: February 5, 2013
    Publication date: February 5, 2015
    Inventor: Mark Edward Brennan Smith
  • Publication number: 20150038684
    Abstract: The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.
    Type: Application
    Filed: February 13, 2013
    Publication date: February 5, 2015
    Applicant: Seattle Children's Hospital (dba Seattle Children's Research Institute)
    Inventor: Michael Jensen
  • Publication number: 20150037328
    Abstract: The present invention provides antibodies and related molecules that bind to chemokine receptor 4 (CXCR4). The invention further provides antibody-drug conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and anti-CXCR4 antibody-drug conjugates for the treatment of a disorder associated with CXCR4 function or expression (e.g., cancer), such as colon, RCC, esophageal, gastric, head and neck, lung, ovarian, pancreatic cancer or hematological cancers.
    Type: Application
    Filed: August 1, 2014
    Publication date: February 5, 2015
    Inventors: Shu-Hui LIU, Flavia Mercer PERNASETTI, Wei-Hsien HO