SG11201506243XA - Tubulysin compounds, methods of making and use - Google Patents

Tubulysin compounds, methods of making and use

Info

Publication number
SG11201506243XA
SG11201506243XA SG11201506243XA SG11201506243XA SG11201506243XA SG 11201506243X A SG11201506243X A SG 11201506243XA SG 11201506243X A SG11201506243X A SG 11201506243XA SG 11201506243X A SG11201506243X A SG 11201506243XA SG 11201506243X A SG11201506243X A SG 11201506243XA
Authority
SG
Singapore
Prior art keywords
making
methods
tubulysin compounds
tubulysin
compounds
Prior art date
Application number
SG11201506243XA
Inventor
Heng Cheng
Qiang Cong
Sanjeev Gangwar
Original Assignee
Bristol Myers Squibb Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of SG11201506243XA publication Critical patent/SG11201506243XA/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1024—Tetrapeptides with the first amino acid being heterocyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/07—Tetrapeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6857—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from lung cancer cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6861—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from kidney or bladder cancer cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6863—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from stomach or intestines cancer cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6869—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Cell Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Oncology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Urology & Nephrology (AREA)
  • Reproductive Health (AREA)
  • Pulmonology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Steroid Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
SG11201506243XA 2013-02-14 2014-02-10 Tubulysin compounds, methods of making and use SG11201506243XA (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361764825P 2013-02-14 2013-02-14
PCT/US2014/015503 WO2014126836A1 (en) 2013-02-14 2014-02-10 Tubulysin compounds, methods of making and use

Publications (1)

Publication Number Publication Date
SG11201506243XA true SG11201506243XA (en) 2015-09-29

Family

ID=50179943

Family Applications (1)

Application Number Title Priority Date Filing Date
SG11201506243XA SG11201506243XA (en) 2013-02-14 2014-02-10 Tubulysin compounds, methods of making and use

Country Status (27)

Country Link
US (5) US9109008B2 (en)
EP (1) EP2956173B1 (en)
JP (1) JP6302490B2 (en)
KR (1) KR102215954B1 (en)
CN (1) CN105073139B (en)
AR (1) AR094784A1 (en)
AU (1) AU2014216539B2 (en)
BR (1) BR112015019432A2 (en)
CA (1) CA2900854C (en)
CY (1) CY1119005T1 (en)
DK (1) DK2956173T3 (en)
EA (1) EA030830B1 (en)
ES (1) ES2628156T3 (en)
HK (1) HK1212209A1 (en)
HR (1) HRP20170888T1 (en)
HU (1) HUE033626T2 (en)
IL (1) IL240475B (en)
LT (1) LT2956173T (en)
MX (1) MX356698B (en)
PL (1) PL2956173T3 (en)
PT (1) PT2956173T (en)
RS (1) RS56169B1 (en)
SG (1) SG11201506243XA (en)
SI (1) SI2956173T1 (en)
TW (1) TW201443083A (en)
UY (1) UY35322A (en)
WO (1) WO2014126836A1 (en)

Families Citing this family (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1789391B1 (en) 2004-07-23 2017-06-28 Endocyte, Inc. Bivalent linkers and conjugates thereof
EP2139523B1 (en) 2007-03-14 2014-10-22 Endocyte, Inc. Conjugates of folate and tubulysin for targeted drug delivery
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
BRPI0812970A2 (en) 2007-06-25 2019-09-24 Endocyte Inc conjugates containing hydrophilic spacers
ES2670874T3 (en) 2011-03-16 2018-06-01 Argenx Bvba Antibodies against CD70
US10080805B2 (en) 2012-02-24 2018-09-25 Purdue Research Foundation Cholecystokinin B receptor targeting for imaging and therapy
US20140080175A1 (en) 2012-03-29 2014-03-20 Endocyte, Inc. Processes for preparing tubulysin derivatives and conjugates thereof
MX2015004757A (en) 2012-10-16 2015-07-17 Endocyte Inc Drug delivery conjugates containing unnatural amino acids and methods for using.
PT2956173T (en) * 2013-02-14 2017-06-26 Bristol Myers Squibb Co Tubulysin compounds, methods of making and use
DK2991683T3 (en) 2013-05-02 2019-11-04 Glykos Finland Oy CONJUGATES OF A GLYCOPROTEIN OR A GLYCAN WITH A TOXIC CHARGE
WO2015095953A1 (en) 2013-12-27 2015-07-02 The Centre For Drug Research And Development Sulfonamide-containing linkage systems for drug conjugates
WO2015095952A1 (en) 2013-12-27 2015-07-02 The Centre For Drug Research And Development Var2csa-drug conjugates
CA2943228C (en) 2014-03-20 2023-03-14 Bristol-Myers Squibb Company Stabilized fibronectin based scaffold molecules
WO2015154064A2 (en) 2014-04-04 2015-10-08 Del Mar Pharmaceuticals Use of dianhydrogalactitol and analogs or derivatives thereof to treat non-small-cell carcinoma of the lung and ovarian cancer
KR20160142392A (en) * 2014-04-11 2016-12-12 메디뮨 엘엘씨 Tubulysin derivatives
US10391168B1 (en) 2014-08-22 2019-08-27 University Of Bern Anti-CD70 combination therapy
GB201416960D0 (en) 2014-09-25 2014-11-12 Antikor Biopharma Ltd Biological materials and uses thereof
US10077287B2 (en) 2014-11-10 2018-09-18 Bristol-Myers Squibb Company Tubulysin analogs and methods of making and use
TWI758928B (en) 2014-11-21 2022-03-21 美商必治妥美雅史谷比公司 Antibodies against cd73 and uses thereof
DK3221346T3 (en) 2014-11-21 2020-10-12 Bristol Myers Squibb Co ANTIBODIES INCLUDING MODIFIED CONSTANT AREAS OF THE HEAVY CHAIN
CN114591420A (en) 2014-11-25 2022-06-07 百时美施贵宝公司 Novel PD-L1 binding polypeptides for imaging
PE20180355A1 (en) 2015-02-25 2018-02-21 Univ Rice William M DEACETOXITUBULISIN H AND ANALOGS OF IT
WO2016144608A1 (en) 2015-03-10 2016-09-15 Bristol-Myers Squibb Company Antibodies conjugatable by transglutaminase and conjugates made therefrom
WO2016196228A1 (en) 2015-05-29 2016-12-08 Bristol-Myers Squibb Company Antibodies against ox40 and uses thereof
US10584160B2 (en) 2015-09-23 2020-03-10 Bristol-Myers Squibb Company Glypican-3-binding fibronectin based scaffold molecules
MX2018006218A (en) * 2015-12-04 2018-09-05 Seattle Genetics Inc Conjugates of quaternized tubulysin compounds.
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
EA201891482A1 (en) 2015-12-21 2018-12-28 Бристол-Маерс Сквибб Компани MODIFIED ANTIBODIES FOR THE SITE-SPECIFIC CONJUGATION
SG10201913033UA (en) 2016-03-04 2020-03-30 Bristol Myers Squibb Co Combination therapy with anti-cd73 antibodies
KR20190005924A (en) 2016-05-10 2019-01-16 브리스톨-마이어스 스큅 컴퍼니 Antibody-drug conjugates of tuburicin analogs with improved stability
US20170326249A1 (en) * 2016-05-10 2017-11-16 Bristol-Myers Squibb Company Antibody-drug conjugate of an anti-glypican-3 antibody and a tubulysin analog, preparation and uses
WO2017218724A1 (en) 2016-06-16 2017-12-21 Bristol-Myers Squibb Company Process and intermediates for making tubulysin analogs
WO2018035391A1 (en) 2016-08-19 2018-02-22 Bristol-Myers Squibb Company Seco-cyclopropapyrroloindole compounds, antibody-drug conjugates thereof, and methods of making and use
WO2018048975A1 (en) 2016-09-09 2018-03-15 Bristol-Myers Squibb Company Use of an anti-pd-1 antibody in combination with an anti-mesothelin antibody in cancer treatment
WO2018075842A1 (en) 2016-10-20 2018-04-26 Bristol-Myers Squibb Company Condensed benzodiazepine derivatives and conjugates made therefrom
MX2019013132A (en) 2017-05-25 2020-01-27 Bristol Myers Squibb Co Antibodies comprising modified heavy constant regions.
GB2567613A (en) * 2017-06-16 2019-04-24 Argenx Bvba Treatment for acute myeloid leukaemia
US10487084B2 (en) 2017-08-16 2019-11-26 Bristol-Myers Squibb Company Toll-like receptor 7 (TLR7) agonists having a heterobiaryl moiety, conjugates thereof, and methods and uses therefor
US10494370B2 (en) 2017-08-16 2019-12-03 Bristol-Myers Squibb Company Toll-like receptor 7 (TLR7) agonists having a pyridine or pyrazine moiety, conjugates thereof, and methods and uses therefor
US10508115B2 (en) 2017-08-16 2019-12-17 Bristol-Myers Squibb Company Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
US10457681B2 (en) 2017-08-16 2019-10-29 Bristol_Myers Squibb Company Toll-like receptor 7 (TLR7) agonists having a tricyclic moiety, conjugates thereof, and methods and uses therefor
US10472361B2 (en) 2017-08-16 2019-11-12 Bristol-Myers Squibb Company Toll-like receptor 7 (TLR7) agonists having a benzotriazole moiety, conjugates thereof, and methods and uses therefor
CA3083345A1 (en) 2017-11-27 2019-05-31 Purdue Pharma L.P. Humanized antibodies targeting human tissue factor
GB201800649D0 (en) 2018-01-16 2018-02-28 Argenx Bvba CD70 Combination Therapy
US11485741B2 (en) 2018-04-24 2022-11-01 Bristol-Myers Squibb Company Macrocyclic toll-like receptor 7 (TLR7) agonists
EA202092747A1 (en) 2018-05-29 2021-03-16 Бристол-Маерс Сквибб Компани MODIFIED SELF-DESTRUCTING FRAGMENTS FOR APPLICATION IN PRODrugs and Conjugates AND METHODS OF APPLICATION AND MANUFACTURING
US11020490B2 (en) 2018-06-22 2021-06-01 Bristol-Myers Squibb Company Antibody-drug conjugate with a tubulysin analog warhead having a stabilized acetate group in the TUV subunit
US11554120B2 (en) 2018-08-03 2023-01-17 Bristol-Myers Squibb Company 1H-pyrazolo[4,3-d]pyrimidine compounds as toll-like receptor 7 (TLR7) agonists and methods and uses therefor
EP3887397A1 (en) 2018-11-28 2021-10-06 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
FI3886914T3 (en) 2018-11-30 2023-05-26 Bristol Myers Squibb Co Antibody comprising a glutamine-containing light chain c-terminal extension, conjugates thereof, and methods and uses
KR20210102334A (en) 2018-12-12 2021-08-19 브리스톨-마이어스 스큅 컴퍼니 Antibodies modified for transglutaminase conjugation, conjugates thereof, and methods and uses
TW202038958A (en) 2018-12-18 2020-11-01 比利時商阿根思公司 Cd70 combination therapy
EA202191769A1 (en) * 2018-12-21 2021-12-08 Регенерон Фармасьютикалз, Инк. TUBULYSINS AND PROTEIN-TUBULYSIN CONJUGATES
CN109796358A (en) * 2019-01-17 2019-05-24 深圳市老年医学研究所 A kind of synthetic method of Tubulysin family compound intermediate TUP
WO2021055306A1 (en) 2019-09-16 2021-03-25 Bristol-Myers Squibb Company Dual capture method for analysis of antibody-drug conjugates
KR20210033435A (en) 2019-09-18 2021-03-26 메콕스큐어메드 주식회사 Novel microorganism capable of producing argyrin and use of the same
CN111454230B (en) * 2020-04-26 2021-12-14 深圳市老年医学研究所 Synthesis method of key intermediate Tuv of natural anticancer drug Tubulysins
EP4171653A2 (en) * 2020-06-24 2023-05-03 Regeneron Pharmaceuticals, Inc. Tubulysins and protein-tubulysin conjugates
KR20220037729A (en) 2020-09-18 2022-03-25 메콕스큐어메드 주식회사 Novel microorganism capable of producing tubulysin and use of the same
WO2024008102A1 (en) * 2022-07-05 2024-01-11 Wuxi Xdc (Shanghai) Co., Ltd. Linker for conjugation

Family Cites Families (83)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1981001145A1 (en) 1979-10-18 1981-04-30 Univ Illinois Hydrolytic enzyme-activatible pro-drugs
US4475196A (en) 1981-03-06 1984-10-02 Zor Clair G Instrument for locating faults in aircraft passenger reading light and attendant call control system
US4447233A (en) 1981-04-10 1984-05-08 Parker-Hannifin Corporation Medication infusion pump
US5144011A (en) 1981-06-26 1992-09-01 Boston University Acidity-sensitive spacer molecule to control the release of pharmaceuticals from molecular carriers
US4631190A (en) 1981-06-26 1986-12-23 Shen Wei C Acidity-sensitive spacer molecule to control the release of pharmaceuticals from molecular carriers
US4439196A (en) 1982-03-18 1984-03-27 Merck & Co., Inc. Osmotic drug delivery system
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
US4447224A (en) 1982-09-20 1984-05-08 Infusaid Corporation Variable flow implantable infusion apparatus
US4487603A (en) 1982-11-26 1984-12-11 Cordis Corporation Implantable microinfusion pump system
US4486194A (en) 1983-06-08 1984-12-04 James Ferrara Therapeutic device for administering medicaments through the skin
US4698420A (en) 1985-02-25 1987-10-06 Xoma Corporation Antibody hybrid molecules and process for their preparation
US4596556A (en) 1985-03-25 1986-06-24 Bioject, Inc. Hypodermic injection apparatus
US5374548A (en) 1986-05-02 1994-12-20 Genentech, Inc. Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor
MX9203291A (en) 1985-06-26 1992-08-01 Liposome Co Inc LIPOSOMAS COUPLING METHOD.
US4894386A (en) 1987-04-15 1990-01-16 Ici Americas Inc. Aliphatic carboxamides
US4941880A (en) 1987-06-19 1990-07-17 Bioject, Inc. Pre-filled ampule and non-invasive hypodermic injection device assembly
US4790824A (en) 1987-06-19 1988-12-13 Bioject, Inc. Non-invasive hypodermic injection device
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
US5064413A (en) 1989-11-09 1991-11-12 Bioject, Inc. Needleless hypodermic injection device
US5312335A (en) 1989-11-09 1994-05-17 Bioject Inc. Needleless hypodermic injection device
US5383851A (en) 1992-07-24 1995-01-24 Bioject Inc. Needleless hypodermic injection device
US6214345B1 (en) 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
TW420681B (en) 1995-12-08 2001-02-01 Lederle Japan Ltd Carbapenem-3-carboxylic acid ester derivatives
DE19638870B4 (en) 1996-09-23 2009-05-14 Helmholtz-Zentrum für Infektionsforschung GmbH Tubulysins, methods for their production and agents containing them
DE60033530T2 (en) 1999-08-24 2007-10-31 Medarex Inc. HUMAN ANTIBODIES TO CTLA-4 AND THEIR USES
DE10008089A1 (en) 2000-02-22 2001-10-31 Biotechnolog Forschung Gmbh Production of tubulysin compounds comprises multi-stage process including condensation of N-methylpipecolinoyl-isoleucine with substituted thiazole-4-carboxylic acid derivative
US20020169125A1 (en) 2001-03-21 2002-11-14 Cell Therapeutics, Inc. Recombinant production of polyanionic polymers and uses thereof
MXPA03011094A (en) 2001-05-31 2004-12-06 Medarex Inc Cytotoxins, prodrugs, linkers and stabilizers useful therefor.
US7091186B2 (en) 2001-09-24 2006-08-15 Seattle Genetics, Inc. p-Amidobenzylethers in drug delivery agents
MXPA04006490A (en) 2002-01-09 2005-06-08 Medarex Inc Human monoclonal antibodies against cd30.
WO2004005327A1 (en) 2002-07-09 2004-01-15 Morphochem Ag Komb Chemie Novel tubulysin analogues
AU2003253048A1 (en) 2002-07-09 2004-01-23 Morphochem Aktiengellschaft Fur Kombinatorische Chemie Tubulysin conjugates
DE10241152A1 (en) 2002-09-05 2004-03-18 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysin biosynthesis genes
DE10254439A1 (en) 2002-11-21 2004-06-03 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysins, manufacturing processes and tubulysin agents
ATE459647T1 (en) 2003-04-15 2010-03-15 Glaxosmithkline Llc HUMAN IL-18 SUBSTITUTION MUTANTS AND THEIR CONJUGATES
GT200400138A (en) 2003-07-22 2005-03-22 RGI ANTIBODIES AND USE OF THE SAME.
WO2005051976A2 (en) 2003-11-20 2005-06-09 Ansata Therapeutics, Inc. Protein and peptide ligation processes and one-step purification processes
US7375078B2 (en) 2004-02-23 2008-05-20 Genentech, Inc. Heterocyclic self-immolative linkers and conjugates
WO2005112919A2 (en) 2004-05-19 2005-12-01 Medarex, Inc. Self-immolative linkers and drug conjugates
RU2402548C2 (en) 2004-05-19 2010-10-27 Медарекс, Инк. Chemical linkers and conjugates thereof
DE102004030227A1 (en) 2004-06-23 2006-01-26 Dömling, Alexander, Dr. Treatment of diseases (e.g. proliferative diseases of tumor cells, ophthalmic diseases and skin diseases) associated with angiogenesis comprises administration of carbamide compounds
KR101270829B1 (en) 2004-09-23 2013-06-07 제넨테크, 인크. Cystein engineered antibodies and conjugates
ES2386366T3 (en) 2005-02-18 2012-08-17 Medarex, Inc. Human monoclonal antibody against prostate specific membrane antigen (PSMA)
JP5249587B2 (en) 2005-02-18 2013-07-31 メダレックス， インク． Monoclonal antibody against prostate specific membrane antigen (PSMA) lacking fucosyl residues
US7714016B2 (en) 2005-04-08 2010-05-11 Medarex, Inc. Cytotoxic compounds and conjugates with cleavable substrates
SI2161336T1 (en) 2005-05-09 2013-11-29 Ono Pharmaceutical Co., Ltd. Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics
EP1899379B1 (en) 2005-06-20 2018-04-11 E. R. Squibb & Sons, L.L.C. Cd19 antibodies and their uses
CN103893778A (en) 2005-08-19 2014-07-02 恩多塞特公司 Multi-drug ligand conjugates
EA016577B1 (en) 2005-09-26 2012-06-29 Медарекс, Инк. Antibody-drug conjugates and use thereof
AU2006294663B2 (en) 2005-09-26 2012-03-22 Medarex, Inc. Human monoclonal antibodies to CD70
EA015324B1 (en) 2005-10-26 2011-06-30 Медарекс, Инк. Methods and compounds for preparing cc-1065 analogs
WO2007059404A2 (en) 2005-11-10 2007-05-24 Medarex, Inc. Duocarmycin derivatives as novel cytotoxic compounds and conjugates
RS52804B (en) 2005-12-08 2013-10-31 Medarex Inc. Human monoclonal antibodies to protein tyrosine kinase 7 (ptk7) and their use
NZ568015A (en) 2005-12-08 2012-03-30 Medarex Inc Human monoclonal antibodies to O8E
KR100869414B1 (en) 2005-12-13 2008-11-21 야마하 가부시키가이샤 Tone plate for keyboard-type tone plate percussion instrument, tone plate fabricating method, tone generator unit of tone plate percussion instrument, and keyboard-type percussion instrument
DK2035554T3 (en) 2006-06-29 2013-06-17 Univ Leland Stanford Junior Cell-free synthesis of proteins containing non-natural amino acids
CN104328086A (en) 2006-09-08 2015-02-04 Ambrx公司 Site Specific Incorporation of Non-Natural Amino Acids by Vertebrate Cells
CN101626782B (en) 2006-12-01 2013-03-27 梅达雷克斯公司 Human antibodies that bind cd22 and uses thereof
EP2097534A4 (en) 2006-12-14 2010-05-12 Medarex Inc Human antibodies that bind cd70 and uses thereof
UY30776A1 (en) 2006-12-21 2008-07-03 Medarex Inc CD44 ANTIBODIES
TWI412367B (en) 2006-12-28 2013-10-21 Medarex Llc Chemical linkers and cleavable substrates and conjugates thereof
JP2010516625A (en) 2007-01-24 2010-05-20 インサート セラピューティクス， インコーポレイテッド Polymer-drug conjugates with tether groups for controlled drug delivery
TW200900059A (en) 2007-02-21 2009-01-01 Medarex Inc Chemical linkers with single amino acids and conjugates thereof
US20100047841A1 (en) 2007-02-27 2010-02-25 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Synthesis of desacetoxytubulysin h and analogs thereof
EP2139523B1 (en) 2007-03-14 2014-10-22 Endocyte, Inc. Conjugates of folate and tubulysin for targeted drug delivery
EP2532673A3 (en) 2007-05-10 2014-01-08 R & D Biopharmaceuticals Gmbh Tubulysine derivatives
BRPI0812970A2 (en) 2007-06-25 2019-09-24 Endocyte Inc conjugates containing hydrophilic spacers
PT2178921E (en) 2007-07-17 2016-03-23 Squibb & Sons Llc Monoclonal antibodies against glypican-3
US8476451B2 (en) 2007-07-20 2013-07-02 The Regents Of The University Of California Tubulysin D analogues
EP3388086B1 (en) 2007-08-17 2020-10-07 Purdue Research Foundation Psma binding ligand-linker conjugates and methods for using
WO2009026274A1 (en) 2007-08-22 2009-02-26 Medarex, Inc. Site-specific attachment of drugs or other agents to engineered antibodies with c-terminal extensions
KR101554848B1 (en) * 2007-10-01 2015-09-21 브리스톨-마이어스 스큅 컴퍼니 Human antibodies that bind mesothelin, and uses thereof
AU2008316835B2 (en) 2007-10-25 2015-07-16 Endocyte, Inc. Tubulysins and processes for preparing
EP2174947A1 (en) 2008-09-25 2010-04-14 Universität des Saarlandes Bioactive pre-tubulysins and use thereof
WO2010087994A2 (en) 2009-01-30 2010-08-05 Whitehead Institute For Biomedical Research Methods for ligation and uses thereof
IT1394860B1 (en) 2009-07-22 2012-07-20 Kemotech S R L PHARMACEUTICAL COMPOUNDS
US8394922B2 (en) * 2009-08-03 2013-03-12 Medarex, Inc. Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
CN102648208B (en) 2009-11-12 2016-04-27 R&D生技药品有限责任公司 Antitubulin
EP2322537A1 (en) 2009-11-12 2011-05-18 R & D Biopharmaceuticals Gmbh Tubulin inhibitors
WO2011069116A1 (en) * 2009-12-04 2011-06-09 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins
EP2409983A1 (en) * 2010-07-19 2012-01-25 Leibniz-Institut für Pflanzenbiochemie (IPB) Tubulysin analogues
IN2014CN04961A (en) 2011-12-05 2015-09-18 Igenica Biotherapeutics Inc
PT2956173T (en) * 2013-02-14 2017-06-26 Bristol Myers Squibb Co Tubulysin compounds, methods of making and use

Also Published As

Publication number Publication date
EA030830B1 (en) 2018-10-31
SI2956173T1 (en) 2017-06-30
US20140227295A1 (en) 2014-08-14
HK1212209A1 (en) 2016-06-10
EA201591317A1 (en) 2015-12-30
JP2016509021A (en) 2016-03-24
PL2956173T3 (en) 2017-09-29
CN105073139B (en) 2019-01-11
TW201443083A (en) 2014-11-16
UY35322A (en) 2014-08-29
EP2956173A1 (en) 2015-12-23
ES2628156T3 (en) 2017-08-01
US20160264624A1 (en) 2016-09-15
DK2956173T3 (en) 2017-07-17
KR20150119086A (en) 2015-10-23
IL240475A0 (en) 2015-09-24
CA2900854A1 (en) 2014-08-21
CN105073139A (en) 2015-11-18
RS56169B1 (en) 2017-11-30
CA2900854C (en) 2017-08-22
MX356698B (en) 2018-06-11
CY1119005T1 (en) 2018-01-10
PT2956173T (en) 2017-06-26
KR102215954B1 (en) 2021-02-15
US8980824B2 (en) 2015-03-17
JP6302490B2 (en) 2018-03-28
WO2014126836A1 (en) 2014-08-21
US20170260232A1 (en) 2017-09-14
IL240475B (en) 2018-03-29
US9109008B2 (en) 2015-08-18
EP2956173B1 (en) 2017-03-29
HRP20170888T1 (en) 2017-09-22
AR094784A1 (en) 2015-08-26
AU2014216539B2 (en) 2017-03-23
LT2956173T (en) 2017-06-26
AU2014216539A1 (en) 2015-10-01
HUE033626T2 (en) 2017-12-28
MX2015010079A (en) 2016-01-25
BR112015019432A2 (en) 2017-08-22
US20140227298A1 (en) 2014-08-14
US9382289B2 (en) 2016-07-05
US20150132324A1 (en) 2015-05-14
US9688721B2 (en) 2017-06-27

Similar Documents

Publication Publication Date Title
HRP20170888T1 (en) Tubulysin compounds, methods of making and use
IL290547A (en) Antibodies and methods of use
IL244495B (en) Anti-alpha-synuclein antibodies and methods of use
GB2535360B (en) Methods of preparing polyhemiaminals and polyhexahydrotriazines
HK1222778A1 (en) Medical device, and the methods of using same
SG11201510561QA (en) Patient interface and aspects thereof
HUE048666T2 (en) Agricultural endophyte-plant compositions, and methods of use
HK1209324A1 (en) Nanozymes, methods of making nanozymes, and methods of using nanozymes
HK1225612A1 (en) Anti-ly6e antibodies and methods of use
GB201301626D0 (en) Composition comprising 15-OHEPA and methods of using the same
EP3054974A4 (en) Glycan-interacting compounds and methods of use
GB201312318D0 (en) Novel methods and compounds
EP2988764A4 (en) Anti-dandruff compositions, and methods of use thereof
HK1220374A1 (en) Compositions and methods for the treatment of carboxyhemoglobinemia
GB201311107D0 (en) Bioorthogonal methods and compounds
PL3055679T3 (en) Fissure-detection agent, method for the production thereof and use of the fissure-detection agent
GB201309375D0 (en) Medical methods and compounds for medical use
ZA201600015B (en) Anti-fibrogenic compounds, methods and uses thereof
EP2980096A4 (en) 2 ,3 ,5 -trihydroxy-androst-6-one and preparation methods and use thereof
IL242818B (en) Il-1beta-il-1ra chimera and methods of using the same
GB201309379D0 (en) Medical methods and compounds for medical use
GB201309376D0 (en) Medical methods and compounds for medical use
GB201310349D0 (en) Composition and method of use thereof
GB201301928D0 (en) Composition and method of use thereof