Conjugated To Nonproteinaceous Bioaffecting Compound (e.g., Conjugated To Cancer-treating Drug, Etc.) Patents (Class 424/181.1)
  • 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
  • Patent number: 10130718
    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: October 4, 2016
    Date of Patent: November 20, 2018
    Assignee: Immunomedics, Inc.
    Inventors: David M. Goldenberg, Serengulam V. Govindan
  • Patent number: 10112999
    Abstract: Provided are antibody drug conjugates that bind PRLR, in particular human PRLR, their methods of making, and uses thereof.
    Type: Grant
    Filed: April 6, 2018
    Date of Patent: October 30, 2018
    Assignee: AbbVie Inc.
    Inventors: Edward B. Reilly, Mark Anderson
  • Patent number: 10071168
    Abstract: In the present disclosure, polymer conjugates, including polymer-antibody-drug conjugates (polymer ADCs) are described, as well as the use of such conjugates to treat human disease. The polymer conjugates can contain a large number of polymer-bound agents, thus effectively increasing the drug antibody ration (DAR) of the antibody significantly beyond the currently available technology. This may be of particular importance when antibodies to low density antigens are used as target antibodies. The described polymer-ADCs have improved pharmacokinetics and solubility relative to traditional ADCs. The linker between agent and the polymer can be tailored to provide release of toxin at the desired site and under the desired conditions within the tumor. An additional feature of the polymer-ADCs of the current disclosure is that a purification moiety can be attached to the polymer backbone to provide ease of purification of the polymer-ADCs.
    Type: Grant
    Filed: July 31, 2015
    Date of Patent: September 11, 2018
    Assignee: Serina Therapeutics, Inc.
    Inventors: Randall W Moreadith, Michael D Bentley, Zhihao Fang, Tacey Viegas
  • Patent number: 10034950
    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 or less, most preferably 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 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: November 14, 2017
    Date of Patent: July 31, 2018
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, Jonathan B. Gale, Nicholas J. Holman, David M. Goldenberg
  • Patent number: 9951133
    Abstract: The invention provides anti-CD33 antibodies and immunoconjugates and methods of using the same.
    Type: Grant
    Filed: June 2, 2016
    Date of Patent: April 24, 2018
    Assignee: GENENTECH, INC.
    Inventors: Shang-Fan Yu, Wei-Ching Liang, Yan Wu, Steven Leong, Andrew Polson
  • Patent number: 9931417
    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: June 29, 2016
    Date of Patent: April 3, 2018
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, Jonathan B. Gale, Nicholas J. Holman, David M. Goldenberg
  • Patent number: 9855344
    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 or less, most preferably 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 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: February 24, 2017
    Date of Patent: January 2, 2018
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, Jonathan B. Gale, Nicholas J. Holman, David M. Goldenberg
  • Patent number: 9797907
    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: April 22, 2016
    Date of Patent: October 24, 2017
    Assignee: Immunomedics, Inc.
    Inventors: David M. Goldenberg, Hans J. Hansen, Chien-Hsing Chang
  • Patent number: 9775915
    Abstract: Provided herein are trioxacarcin-antibody drug conjugates of Formula (A): and pharmaceutically acceptable salts thereof, comprising at least one instance of the group -L1-(A-L2)a-B attached thereto, wherein a is an integer between 1 and 10, inclusive, L1 is absent or is a linking group, A is a moiety formed from the reaction of two complimentary groups (X and Y), L2 is absent or is another linking group, and B is an antibody or antibody fragment. Also provided are methods of preparing these antibody-drug conjugates, pharmaceutically acceptable compositions thereof, and methods of their use and treatment. Further provided are precursors to the trioxacarcin-antibody drug conjugates, novel trioxacarcins without an antibody conjugated thereto, pharmaceutical compositions thereof, and methods of their use and treatment.
    Type: Grant
    Filed: November 26, 2013
    Date of Patent: October 3, 2017
    Assignee: President and Fellows of Harvard College
    Inventors: Andrew G. Myers, Daniel J. Smaltz, Andreas Schumacher
  • Patent number: 9777071
    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: October 21, 2016
    Date of Patent: October 3, 2017
    Assignee: ABBVIE STEMCENTRX LLC
    Inventors: Laura Saunders, Deepti Rokkam, David Liu, Mandy Boontanrart
  • Patent number: 9738602
    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: Grant
    Filed: December 18, 2015
    Date of Patent: August 22, 2017
    Assignee: Wyeth LLC
    Inventors: George Anello Chiarello, Ayman Sahli
  • Patent number: 9724427
    Abstract: The invention provides anti-Ly6E antibodies, immunoconjugates and methods of using the same.
    Type: Grant
    Filed: May 20, 2013
    Date of Patent: August 8, 2017
    Assignee: Genentech, Inc.
    Inventors: Chie Sakanaka, Peter Chang
  • Patent number: 9629926
    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 or less, most preferably 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 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: May 23, 2016
    Date of Patent: April 25, 2017
    Assignee: Immunomedics, Inc.
    Inventors: Serengulam V. Govindan, Jonathan B. Gale, Nicholas J. Holman, David M. Goldenberg
  • Patent number: RE47103
    Abstract: Antibody drug conjugates (ADC's) that bind to 158P1D7 protein and variants thereof are described herein. 158P1D7 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in glioblastoma, lung cancer, bladder cancer, and breast cancer. Consequently, the ADC's of the invention provide a therapeutic composition for the treatment of cancer.
    Type: Grant
    Filed: March 2, 2017
    Date of Patent: October 30, 2018
    Assignees: AGENSYS, INC., SEATTLE GENETICS, INC.
    Inventors: Robert Kendall Morrison, Zili An, Karen Jane Meyrick Morrison, Josh Snyder, Xiao-Chi Jia