Conjugated To Nonproteinaceous Bioaffecting Compound (e.g., Conjugated To Cancer-treating Drug, Etc.) Patents (Class 424/181.1)
  • Patent number: 11439620
    Abstract: The present invention relates to combination therapy with ADCs against a tumor-associated antigen, such as Trop-2, and drugs, such as microtubule inhibitors and/or PARP inhibitors. Where ADCs are used, they preferably incorporate SN-38 or another drug that induces DNA strand breaks. Preferably, the combination of ADC and PARPi or microtubule inhibitor exhibits synergistic effects against the cancer. The combination therapy 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: November 29, 2018
    Date of Patent: September 13, 2022
    Assignee: Immunomedics, Inc.
    Inventors: David M. Goldenberg, Thomas M. Cardillo
  • Patent number: 11376269
    Abstract: The present invention relates to pharmaceutical compositions for use in the treatment of chemoresistant acute myeloid leukemia (AML). The inventors have established a powerful preclinical model to screen in vivo responses to conventional genotoxics and to mimic the chemoresistance and minimal residual disease as observed in AML patients after chemotherapy. The inventors showed that cytarabine-resistance mechanism involves the CD39-dependent crosstalk between energetic niche and AML mitochondrial functions through CD39-P2Y13-cAMP-PKA signaling axis. In particular, the present invention relates to an inhibitor of the CD39-P2Y13-cAMP-PKA signaling axis for use in a method of treating chemoresistant acute myeloid leukemia (AML) in a patient in need thereof comprising administering to the patient a therapeutically effective amount of said inhibitor.
    Type: Grant
    Filed: May 5, 2017
    Date of Patent: July 5, 2022
    Assignees: INSERM, UNIVERSITE PAUL SABATIER TOULOUSE III, CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE
    Inventors: Jean-Emmanuel Sarry, Christian Recher, Fabienne De Toni-Costes, Nesrine Aroua
  • Patent number: 11365265
    Abstract: The present invention relates to combinations of anti-C5 antibodies and antigen-binding fragments which have been determined to exhibit superior activity relative to that of a single anti-C5 antibody or fragment. The combinations include anti-C5 antibodies and antigen-binding fragments which do not compete with one another from C5 binding. Bispecific antibodies comprising antigen-binding domains which do not compete and/or bind the same epitope on C5 are also provided. Compositions and therapeutic methods relating to such anti-C5 combinations and bispecific antibodies are provided herein.
    Type: Grant
    Filed: December 12, 2018
    Date of Patent: June 21, 2022
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventor: Kishor Devalaraja-Narashimha
  • Patent number: 11364303
    Abstract: The invention relates to polypeptides, antibodies, and antigen-binding fragments thereof, that comprise an engineered cysteine for site-specific conjugation.
    Type: Grant
    Filed: September 24, 2018
    Date of Patent: June 21, 2022
    Assignee: Pfizer Inc.
    Inventors: Madan Katragadda, Russell Dushin, Lawrence Nathan Tumey
  • Patent number: 11357864
    Abstract: The present invention provides antibody drug conjugates, wherein an antibody or antibody fragment that specifically binds to human cKIT is linked to a drug moiety, optionally through a linker. The present invention further provides pharmaceutical compositions comprising the antibody drug conjugates; and methods of making and using such pharmaceutical compositions for ablating hematopoietic stem cells in a patient in need thereof.
    Type: Grant
    Filed: December 19, 2017
    Date of Patent: June 14, 2022
    Assignee: Novartis AG
    Inventors: Ben Wen, Anthony E. Boitano, Matthew Burger, Susan E. Cellitti, Michael P. Cooke, Catrin Finner, Bernhard Hubert Geierstanger, Yunho Jin, Si Tuen Lee-Hoeflich, HongNgoc Thi Pham, Siew Ho Schleyer, Kathrin Tissot, Tetsuo Uno
  • Patent number: 11325980
    Abstract: The invention provides methods of treating a subject having or at risk of cancer by administering a LIV-1 antibody drug conjugate and a chemotherapeutic.
    Type: Grant
    Filed: March 15, 2017
    Date of Patent: May 10, 2022
    Assignee: SEAGEN INC.
    Inventors: Django Sussman, Fu Li, Ana Kostic
  • Patent number: 11311626
    Abstract: The present invention relates to an antibody-drug conjugate (ADC) and a composition containing the conjugate for use in treating cancer. According to the present invention, provided are an ADC of an antibody specific to insoluble fibrin and a drug in which a linker linking the antibody and the drug has a plasmin cleavage sequence, and a pharmaceutical composition containing the ADC for use in treating cancer.
    Type: Grant
    Filed: April 27, 2018
    Date of Patent: April 26, 2022
    Assignees: NATIONAL CANCER CENTER JAPAN, RIN INSTITUTE INC.
    Inventors: Yasuhiro Matsumura, Shino Manabe, Hirobumi Fuchigami
  • Patent number: 11208496
    Abstract: Anti-CD19 B4 antibodies with modified variable regions are disclosed. The modified anti-CD19 variable region polypeptides have alterations to one or more framework regions or complementarity determining regions of the heavy chain variable region or light chain variable region, thereby to reduce a T-cell response.
    Type: Grant
    Filed: September 10, 2018
    Date of Patent: December 28, 2021
    Assignee: Cancer Research Technology LTD.
    Inventors: Michael Super, Jonathan Davis, Pascal Andre Stein
  • Patent number: 11180451
    Abstract: The present disclosure provides conjugate structures and hydrazinyl-pyrrolo compound structures used to produce these conjugates. The disclosure also encompasses methods of production of such conjugates, as well as methods of using the same.
    Type: Grant
    Filed: December 20, 2019
    Date of Patent: November 23, 2021
    Assignee: Redwood Bioscience, Inc.
    Inventors: David Rabuka, Aaron Edward Albers, Romas Alvydas Kudirka, Albert W. Garofalo
  • Patent number: 11167040
    Abstract: In some aspects, the invention relates to an antibody-drug conjugate, comprising an antibody; a linker; and at least two active agents. In preferred embodiments, the linker comprises a peptide sequence of a plurality of amino acids, and at least two of the active agents are covalently coupled to side chains of the amino acids. The antibody-drug conjugate may comprise a self-immolative group, preferably two-self-immolative groups. The linker may comprise an O-substituted oxime, e.g., wherein the oxygen atom of the oxime is substituted with a group that covalently links the oxime to the active agent; and the carbon atom of the oxime is substituted with a group that covalently links the oxime to the antibody.
    Type: Grant
    Filed: November 23, 2016
    Date of Patent: November 9, 2021
    Assignee: LegoChem Biosciences, Inc.
    Inventors: Yong Zu Kim, Yeong Soo Oh, Jeiwook Chae, Ho Young Song, Chul-Woong Chung, Yun Hee Park, Hyo Jung Choi, Kyung Eun Park, Hyoungrae Kim, Jinyeong Kim, Ji Young Min, Sung Min Kim, Byung Soo Lee, Dong Hyun Woo, Ji Eun Jung, Su In Lee
  • Patent number: 11135302
    Abstract: IgA-based Fc-folate conjugates as a treatment for cancer are provided. The conjugates utilize only the Fc portion of IgA to target its receptor on neutrophils (Fc?R1) to elicit antibody-dependent cellular-cytotoxicity (ADCC).
    Type: Grant
    Filed: May 10, 2019
    Date of Patent: October 5, 2021
    Assignee: Wayne State University
    Inventor: Cecilia Speyer
  • Patent number: 11104673
    Abstract: This invention relates to quaternary amine linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.
    Type: Grant
    Filed: November 27, 2019
    Date of Patent: August 31, 2021
    Assignee: Genentech, Inc.
    Inventors: John A. Flygare, Thomas Pillow, Leanna Staben
  • Patent number: 11098076
    Abstract: Disclosed is a compound of formula (I): wherein R1, R2, R3, and are as defined herein. Also disclosed are methods for increasing mammalian cell NAD+ production and improving mitochondrial cell densities comprising administering to a cell the compound or a salt thereof.
    Type: Grant
    Filed: August 26, 2019
    Date of Patent: August 24, 2021
    Assignee: Cornell University
    Inventors: Anthony Sauve, Farheen Sultana Mohammed, Yue Yang
  • Patent number: 11090322
    Abstract: The invention provides antibody-drug conjugates comprising an antibody conjugated to an anthracycline drug moiety via a disulfide linker, anthracycline disulfide intermediates, and methods of using the antibody-drug conjugates.
    Type: Grant
    Filed: November 1, 2018
    Date of Patent: August 17, 2021
    Assignee: Genentech, Inc.
    Inventors: John A. Flygare, Thomas H. Pillow
  • Patent number: 11066468
    Abstract: The invention relates to therapeutic conjugates with improved ability to target various cancer cells containing a targeting moiety and a therapeutic moiety. The targeting and therapeutic moieties are linked via an acid cleavable linkage that increases therapeutic efficacy of the immunoconjugate.
    Type: Grant
    Filed: March 6, 2019
    Date of Patent: July 20, 2021
    Assignee: Immunomedics, Inc.
    Inventor: Serengulam V. Govindan
  • Patent number: 11052111
    Abstract: In an aspect, the present invention relates generally to the field of treating disease with CAR devices, Smart CAR devices, DE CAR devices, and/or Smart-DE CAR devices. The present invention also relates generally to the genetic modification of cytotoxic T-lymphocytes to reduce target cell killing by apoptosis and/or increase production of lytic proteins at desired times. In an aspect, the invention relates to the use of these genetically modified T-lymphocytes and/or natural killer cells with CAR devices, Smart CAR devices, DE CAR devices, and/or Smart-DE CAR devices to enhance the immune response against a disease.
    Type: Grant
    Filed: December 5, 2016
    Date of Patent: July 6, 2021
    Assignee: Chimera Bioengineering, Inc.
    Inventors: Benjamin Wang, Gusti Zeiner
  • Patent number: 11052081
    Abstract: The present invention relates to therapeutic ADCs comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. The ADC may be administered at a dosage of between 4 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, most preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the ADC 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. Preferably, the ADC is administered in combination with one or more other therapeutic agents, such as a PARP inhibitor, a microtubule inhibitor, a Bruton kinase inhibitor or a PI3K inhibitor. Most preferably, the ADC is of use for treating a Trop-2 expressing cancer, such as metastatic urothelial cancer.
    Type: Grant
    Filed: July 29, 2019
    Date of Patent: July 6, 2021
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, David M. Goldenberg
  • Patent number: 11046762
    Abstract: Charged or pro-charged cross-linking moieties and conjugates of cell binding agents and drugs comprising the charged or pro-charged cross-linking moieties and method of making the same.
    Type: Grant
    Filed: October 14, 2019
    Date of Patent: June 29, 2021
    Assignee: IMMUNOGEN, INC.
    Inventors: Ravi V. J. Chari, Robert Yongxin Zhao, Yelena Kovtun, Rajeeva Singh, Wayne C. Widdison
  • Patent number: 11008398
    Abstract: It is intended to provide an antitumor drug having an excellent therapeutic effect, which is excellent in terms of antitumor effect and safety. There is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an anti-TROP2 antibody via a linker having a structure represented by the following formula: -L1-L2-LP-NH—(CH2)n1-La-(CH2)n2-C(?O)— wherein the anti-TROP2 antibody is connected to the terminal of L1, and the antitumor compound is connected to the carbonyl group of the —(CH2)n2-C(?O)— moiety with the nitrogen atom of the amino group at position 1 as a connecting position.
    Type: Grant
    Filed: January 24, 2019
    Date of Patent: May 18, 2021
    Assignees: DAIICHI SANKYO COMPANY, LIMITED, SAPPORO MEDICAL UNIVERSITY
    Inventors: Toshinori Agatsuma, Shu Takahashi, Jun Hasegawa, Daisuke Okajima, Hirofumi Hamada, Miki Yamaguchi
  • Patent number: 10988539
    Abstract: The present invention relates to combination therapy with drugs, such as Bruton's tyrosine kinase inhibitors or PI3K inhibitors, with antibodies or ADCs against HLA-DR. Where ADCs are used, they preferably incorporate SN-38 or pro-2PDOX. The ADC may be administered at a dosage of between 1 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg. The combination therapy 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. Preferably, the combination therapy has an additive effect on inhibiting tumor growth. Most preferably, the combination therapy has a synergistic effect on inhibiting tumor growth.
    Type: Grant
    Filed: July 20, 2018
    Date of Patent: April 27, 2021
    Assignee: Immunomedics, Inc.
    Inventors: David M. Goldenberg, Thomas M. Cardillo
  • Patent number: 10940178
    Abstract: Methods for the treatment of CD30-expressing cancers are provided. The methods comprise administering to a subject in need thereof a weekly dose of from about 0.8 mg/kg to about 1.8 mg/kg of an antibody-drug conjugate compound having formula (I); or a pharmaceutically acceptable salt thereof; wherein: mAb is an anti-CD30 antibody unit, S is a sulfur atom of the antibody, A- is a Stretcher unit, and p is from about 3 to about 5.
    Type: Grant
    Filed: June 17, 2020
    Date of Patent: March 9, 2021
    Assignee: SEAGEN INC.
    Inventors: Eric Sievers, Dana Kennedy
  • Patent number: 10918721
    Abstract: The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. In preferred embodiments, the antibody may be an hRS7 antibody. The methods and compostions are of use to treat Trop-2 expressing cancers in human patients, preferably in patients who are resistant to or relapsed from at least one prior anti-cancer therapy, more preferably in patients who are resistant to or relapsed from treatment with irinotecan. The immunoconjugate may be administered at a dosage of 3 mg/kg to 18 mg/kg, preferably 8 to 12 mg/kg, more preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size and reduce or eliminate metastases.
    Type: Grant
    Filed: October 9, 2018
    Date of Patent: February 16, 2021
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, David M. Goldenberg
  • Patent number: 10898570
    Abstract: The present invention is directed to a combination therapy involving an anti-HER2 antibody-drug conjugate and a selective Bcl-2 inhibitor for the treatment of a patient suffering from cancer, particularly, a HER2-expressing cancer.
    Type: Grant
    Filed: December 20, 2017
    Date of Patent: January 26, 2021
    Assignee: Genentech, Inc.
    Inventors: Gail Lewis Phillips, Deepak Sampath, Ingrid Wertz
  • Patent number: 10870706
    Abstract: The present invention is directed to novel bifunctional CTI-CTI and CBI-CTI dimers of the formula: F1-L1-T-L2-F2 where F1, L1, T, L2 and F2 are as defined herein, useful for the treatment for proliferative diseases, where the inventive dimers can function as stand-alone drugs, payloads in antibody-drug-conjugates (ADCs), and linker-payload compounds useful in connection with the production or administration of such ADCs; and to compositions including the aforementioned dimers, linker-payloads and ADCs, and methods for using these dimers, linker-payloads and ADCs, to treat pathological conditions including cancer.
    Type: Grant
    Filed: March 15, 2016
    Date of Patent: December 22, 2020
    Assignee: PFIZER INC.
    Inventors: Andreas Maderna, Chakrapani Subramanyam, Lawrence N. Tumey, Zecheng Chen, Jeffrey M. Casavant
  • Patent number: 10793527
    Abstract: The present invention discloses a compound of the formula (I), which acts as an agonist of adenosine monophosphate-activated protein kinase, which induce phosphorylation and activation of AMPK?, thereby further regulating downstream signaling pathways, inhibiting growth and proliferation of liver cancer cells and breast cancer cells, and also inducing apoptosis of adipocytes. Therefore, the compound provided by the present invention can be utilised for treatment and preparation of pharmaceutical composition for cancer, and lipid metabolism-related diseases or syndromes mediated by AMPK.
    Type: Grant
    Filed: September 6, 2017
    Date of Patent: October 6, 2020
    Assignee: NATIONAL YANG-MING UNIVERSITY
    Inventors: Chung-Wai Shiau, Jung-Chen Su, Yan-Ju Lin, Jui-Wen Huang
  • Patent number: 10751420
    Abstract: The present invention concerns improved methods and compositions for preparing SN-38 conjugates of proteins or peptides, preferably immunoconjugates of antibodies or antigen-binding antibody fragments. More preferably, the SN-38 is attached to the antibody or antibody fragment using a CL2A linker, with 1-12, more preferably 6-8, alternatively 1-5 SN-38 moieties per antibody or antibody fragment. Most preferably, the immunoconjugate is prepared in large scale batches, with various modifications to the reaction scheme disclosed herein to optimize yield and recovery in large scale. Other embodiments concern optimized dosages and/or schedules of administration of immunoconjugate to maximize efficacy for disease treatment and minimize side effects of administration.
    Type: Grant
    Filed: October 11, 2018
    Date of Patent: August 25, 2020
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, Jonathan B. Gale, Nicholas J. Holman, David M. Goldenberg
  • Patent number: 10744129
    Abstract: The present invention relates to treatment of SCLC with therapeutic ADCs comprising a drug attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. Preferably, the drug is SN-38. More preferably, the antibody is an hRS7 antibody and the ADC is sacituzumab govitecan. The ADC may be administered at a dosage of between 4 mg/kg and 16 mg/kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg/kg, mostly preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the ADC 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. Surprisingly, the ADC is effective to treat cancers that are refractory to or relapsed from irinotecan or topotecan. Preferably, the ADC is administered as a combination therapy with one or more other anti-cancer treatments, such as carboplatin or cisplatinum.
    Type: Grant
    Filed: February 21, 2018
    Date of Patent: August 18, 2020
    Assignee: Immunomedics, Inc.
    Inventors: David M. Goldenberg, Serengulam V. Govindan
  • Patent number: 10729738
    Abstract: The invention relates generally to disulfide drug conjugates wherein a linker comprising a sulfur-bearing carbon atom substituted with at least one hydrocarbyl or substituted hydrocarbyl is conjugated by a disulfide bond to a cysteine sulfur atom of a targeting carrier, and wherein the linker is further conjugated to a drug moiety. The invention further relates to activated linker-drug conjugates suitable for conjugation to a targeting carrier by a disulfide bond. The invention further relates to methods for preparing hindered disulfide drug conjugates.
    Type: Grant
    Filed: October 14, 2016
    Date of Patent: August 4, 2020
    Assignee: Genentech, Inc.
    Inventors: Peter Dragovich, Zhonghua Pei, Thomas Pillow, Jack Sadowsky, Jinhua Chen, John Wai
  • Patent number: 10722549
    Abstract: Methods for the treatment of CD30-expressing cancers are provided. The methods comprise administering to a subject in need thereof a weekly dose of from about 0.8 mg/kg to about 1.8 mg/kg of an antibody-drug conjugate compound having formula (I); or a pharmaceutically acceptable salt thereof; wherein: mAb is an anti-CD30 antibody unit, S is a sulfur atom of the antibody, A- is a Stretcher unit, and p is from about 3 to about 5.
    Type: Grant
    Filed: October 7, 2019
    Date of Patent: July 28, 2020
    Assignee: SEATTLE GENETICS, INC.
    Inventors: Eric Sievers, Dana Kennedy
  • Patent number: 10709701
    Abstract: The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-HLA-DR antibody or antigen-binding antibody fragment. The immunoconjugate may be administered at a dosage of between 3 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, more preferably 8, 10 or 12 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. The methods and compositions are particularly useful for treating AML, ALL or multiple myeloma.
    Type: Grant
    Filed: November 30, 2018
    Date of Patent: July 14, 2020
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, Thomas M. Cardillo, David M. Goldenberg
  • Patent number: 10682347
    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: September 28, 2018
    Date of Patent: June 16, 2020
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, David M. Goldenberg
  • Patent number: 10675357
    Abstract: The present invention relates to antibodies having specificity to nectin-4 and uses thereof.
    Type: Grant
    Filed: September 7, 2016
    Date of Patent: June 9, 2020
    Assignees: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE, UNIVERSITÉ D'AIX MARSEILLE, CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS), INSTITUT JEAN PAOLI & IRENE CALMETTES
    Inventors: Marc Lopez, Daniel Olive
  • Patent number: 10653793
    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 Trop-2 or CEACAM5 and the immunoconjugate may be administered at a dosage of between 4 mg/kg and 16 mg/kg, preferably 4, 6, 8, 9, 10, 12, or 16 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. Surprisingly, the immunoconjugate is effective to treat cancers that are refractory to or relapsed from irinotecan.
    Type: Grant
    Filed: September 27, 2018
    Date of Patent: May 19, 2020
    Assignee: Immunomedics, Inc.
    Inventors: David M. Goldenberg, Serengulam V. Govindan
  • Patent number: 10604483
    Abstract: The present disclosure provides conjugate structures and hydrazinyl-pyrrolo compound structures used to produce these conjugates. The disclosure also encompasses methods of production of such conjugates, as well as methods of using the same.
    Type: Grant
    Filed: June 7, 2019
    Date of Patent: March 31, 2020
    Assignee: Redwood Bioscience, Inc.
    Inventors: David Rabuka, Aaron Edward Albers, Romas Alvydas Kudirka, Albert W. Garofalo
  • Patent number: 10576164
    Abstract: Conjugate compounds of formula (A): wherein: R2 is where R36a and R36b are independently selected from H, F, C1-4 saturated alkyl, C2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C1-4 alkyl amido and C1-4 alkyl ester; or, when one of R36a and R36b is H, the other is selected from nitrile and a C1-4 alkyl ester; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, Me3Sn and halo; R7 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, Me3Sn and halo; Y is selected from formulae A1, A2, A3, A4, A5 and A6: L is a linker connected to a cell binding agent; CBA is the cell binding agent; n is an integer selected in the range of 0 to 48; RA4 is a C1-6 alkylene group; either (a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl; or (b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (c) R10 is H and R11 is OSOzM, wher
    Type: Grant
    Filed: October 17, 2017
    Date of Patent: March 3, 2020
    Assignees: MedImmune Limited, Genentech, Inc.
    Inventors: Philip Wilson Howard, John A. Flygare, Thomas Pillow, Binqing Wei
  • Patent number: 10570192
    Abstract: The invention provides anti-wall teichoic acid antibodies and antibiotic conjugates thereof, and methods of using the same.
    Type: Grant
    Filed: September 28, 2017
    Date of Patent: February 25, 2020
    Assignee: Genentech, Inc.
    Inventors: Eric J. Brown, Martine Darwish, John Flygare, Wouter Hazenbos, Byoung Chul Lee, Sophie M. Lehar, Sanjeev Mariathasan, John Hiroshi Morisaki, Thomas H. Pillow, Leanna Staben, Richard Vandlen, Klaus Koefoed, Magnus Strandh, Peter S. Andersen
  • Patent number: 10519249
    Abstract: Herein is reported a conjugate of a haptenylated polypeptide toxin and an anti-hapten antibody, wherein a disulfide bond is formed between a cysteine residue either before or after the lysine residue that is used for hapten-conjugation and a cysteine residue in the CDR2 of the antibody, whereby the CDR2 is determined according to Kabat.
    Type: Grant
    Filed: July 1, 2016
    Date of Patent: December 31, 2019
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Ulrich Brinkmann, Eike Hoffmann, Stefan Dengl, Klaus Mayer
  • Patent number: 10494431
    Abstract: Charged or pro-charged cross-linking moieties and conjugates of cell binding agents and drugs comprising the charged or pro-charged cross-linking moieties and method of making the same.
    Type: Grant
    Filed: March 5, 2018
    Date of Patent: December 3, 2019
    Assignee: IMMUNOGEN, INC.
    Inventors: Ravi V. J. Chari, Robert Yongxin Zhao, Yelena Kovtun, Rajeeva Singh, Wayne C. Widdison
  • Patent number: 10478469
    Abstract: Methods for the treatment of CD30-expressing cancers are provided. The methods comprise administering to a subject in need thereof a weekly dose of from about 0.8 mg/kg to about 1.8 mg/kg of an antibody-drug conjugate compound having formula (I); or a pharmaceutically acceptable salt thereof; wherein: mAb is an anti-CD30 antibody unit, S is a sulfur atom of the antibody, A? is a Stretcher unit, and p is from about 3 to about 5.
    Type: Grant
    Filed: April 4, 2019
    Date of Patent: November 19, 2019
    Assignee: SEATTLE GENETICS, INC.
    Inventors: Eric Sievers, Dana Kennedy
  • Patent number: 10436788
    Abstract: Described herein are compositions and methods of use of anti-Trop-2 antibodies or antigen-binding fragment thereof to isolate, enrich, detect, diagnose and/or characterize circulating tumor cells (CTCs) from patients with a Trop-2 positive cancer. Preferably, the antibody is an RS7, 162-46.2 or MAB650 antibody. The compositions and methods are of use to detect, diagnose and/or treat metastatic Trop-2+ cancers, such as breast, ovarian, cervical, endometrial, lung, prostate, colon, rectum, stomach, esophageal, bladder, renal, pancreatic, thyroid, epithelial or head-and-neck cancer.
    Type: Grant
    Filed: September 18, 2017
    Date of Patent: October 8, 2019
    Assignee: Immunomedics, Inc.
    Inventors: David M. Goldenberg, Hans J. Hansen, Chien-Hsing Chang
  • Patent number: 10413539
    Abstract: The present invention relates to therapeutic ADCs comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. The ADC may be administered at a dosage of between 4 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, most preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the ADC 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. Preferably, the ADC is administered in combination with one or more other therapeutic agents, such as a PARP inhibitor, a microtubule inhibitor, a Bruton kinase inhibitor or a PI3K inhibitor. Most preferably, the ADC is of use for treating a Trop-2 expressing cancer, such as metastatic urothelial cancer.
    Type: Grant
    Filed: November 22, 2017
    Date of Patent: September 17, 2019
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, David M. Goldenberg
  • Patent number: 10301365
    Abstract: The present invention provides isolated Met e 1 polypeptides and nucleic acids encoding the isolated polypeptides that can prevent and/or alleviate an allergic response to shellfish tropomyosin. The polypeptides are based on the shrimp tropomyosin Met e 1 protein and have been modified to act as hypoallergens. The Met e 1 hypoallergens have low to no IgE reactivity or allergenicity and are useful for prophylactic and/or therapeutic treatment of shellfish allergy in subject in need thereof.
    Type: Grant
    Filed: October 3, 2016
    Date of Patent: May 28, 2019
    Assignees: The Chinese University of Hong Kong, The Regents of the University of California
    Inventors: Ka Hou Chu, Patrick S. C. Leung, Yee Yan Christine Wai, Yat Hin Nicki Leung
  • Patent number: 10232040
    Abstract: Provided herein are methods of treating non-small cell lung cancers comprising administering an effective amount of MEDI4736 or an antigen-binding fragment thereof and tremelimumab or an antigen-binding fragment thereof.
    Type: Grant
    Filed: May 12, 2015
    Date of Patent: March 19, 2019
    Assignee: MEDIMMUNE, LLC
    Inventors: Rajesh Narwal, Paul Robbins, Joyson Karakunnel, Mohammed Dar
  • Patent number: 10220090
    Abstract: The present invention relates to BCMA (B-Cell Maturation Antigen) antigen binding proteins, such as antibodies, polynucleotide sequences encoding said antigen binding proteins, and compositions and methods for diagnosing and treating diseases. The present invention also relates to BCMA antibody drug conjugates.
    Type: Grant
    Filed: December 11, 2015
    Date of Patent: March 5, 2019
    Assignee: Amgen Inc.
    Inventors: Richard J. Armitage, Michelle Blake, William C. Fanslow, III, Jason Charles O'Neill, Gunasekaran Kannan, Jiangchun Xu, Mark Edward Tometsko
  • Patent number: 10206918
    Abstract: The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-HLA-DR antibody or antigen-binding antibody fragment. The immunoconjugate may be administered at a dosage of between 3 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, more preferably 8, 10 or 12 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. The methods and compositions are particularly useful for treating AML, ALL or multiple myeloma.
    Type: Grant
    Filed: August 4, 2017
    Date of Patent: February 19, 2019
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, Thomas M. Cardillo, David M. Goldenberg
  • Patent number: 10195175
    Abstract: The present invention relates to combination therapy with ADCs against a tumor-associated antigen, such as Trop-2, and drugs, such as microtubule inhibitors and/or PARP inhibitors. Where ADCs are used, they preferably incorporate SN-38 or another drug that induces DNA strand breaks. Preferably, the combination of ADC and PARPi or microtubule inhibitor exhibits synergistic effects against the cancer. The combination therapy 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: April 6, 2017
    Date of Patent: February 5, 2019
    Assignee: Immunomedics, Inc.
    Inventors: David M. Goldenberg, Thomas M. Cardillo
  • Patent number: 10189910
    Abstract: Provided herein are novel anti-DPEP3 antibodies and antibody drug conjugates (ADC), including derivatives thereof, and methods of using the same to treat proliferative disorders.
    Type: Grant
    Filed: June 13, 2016
    Date of Patent: January 29, 2019
    Assignee: AbbVie Stemcentrx LLC
    Inventors: Laura Saunders, Deepti Rokkam, David Liu, Mandy Boontanrart
  • Patent number: 10174094
    Abstract: The present invention relates to the use of a compound containing a moiety of formula (I) as a reagent for linking a compound of formula R1—H which comprises a first functional moiety of formula F1 to a second functional moiety of formula F2 wherein X, X?, Y, R1, F1 and F2 are as defined herein. The present invention also provides related processes and products. The present invention is useful for creating functional conjugate compounds, and specifically conjugates in which at least one of the constituent molecules carries a thiol group.
    Type: Grant
    Filed: February 17, 2016
    Date of Patent: January 8, 2019
    Assignee: UCL Business Plc
    Inventors: Mark Smith, Stephen Caddick, James Baker, Vijay Chudasama
  • Patent number: 10155812
    Abstract: This present invention relates to compounds (e.g., TM4SF1 binding proteins, e.g., anti-TM4SF1 antibodies) that specifically bind to a polypeptide at an epitope including an amino acid sequence of SEQ ID NO: 1. In particular, the compounds of the invention are capable of being internalized into a TM4SF1-expressing cell (e.g., a tumor cell or an angiogenic vasculature endothelial cell) following binding to the epitope of including the amino acid sequence of SEQ ID NO: 1. The invention also provides methods of treating a subject having a disorder associated with pathological angiogenesis with the compounds of the invention.
    Type: Grant
    Filed: April 6, 2016
    Date of Patent: December 18, 2018
    Assignee: Beth Israel Deaconess Medical Center, Inc.
    Inventors: Shou-Ching S. Jaminet, Harold F. Dvorak
  • Patent number: 10143756
    Abstract: The present invention concerns improved methods and compositions for preparing SN-38 conjugates of proteins or peptides, preferably immunoconjugates of antibodies or antigen-binding antibody fragments. More preferably, the SN-38 is attached to the antibody or antibody fragment using a CL2A linker, with 1-12, more preferably 6-8, alternatively 1-5 SN-38 moieties per antibody or antibody fragment. Most preferably, the immunoconjugate is prepared in large scale batches, with various modifications to the reaction scheme disclosed herein to optimize yield and recovery in large scale. Other embodiments concern optimized dosages and/or schedules of administration of immunoconjugate to maximize efficacy for disease treatment and minimize side effects of administration.
    Type: Grant
    Filed: January 29, 2018
    Date of Patent: December 4, 2018
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, Jonathan B. Gale, Nicholas J. Holman, David M. Goldenberg