WO1996040261A1 - Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates - Google Patents

Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates Download PDF

Info

Publication number
WO1996040261A1
WO1996040261A1 PCT/US1996/006738 US9606738W WO9640261A1 WO 1996040261 A1 WO1996040261 A1 WO 1996040261A1 US 9606738 W US9606738 W US 9606738W WO 9640261 A1 WO9640261 A1 WO 9640261A1
Authority
WO
WIPO (PCT)
Prior art keywords
coor
conhr
radical
bond
trivalent
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US1996/006738
Other languages
English (en)
French (fr)
Inventor
Martin Paul Kunstmann
Irwin Jack Hollander
Philip Hamann
Arthur Kunz
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wyeth Holdings LLC
Original Assignee
American Cyanamid 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
Priority to AU57423/96A priority Critical patent/AU703862B2/en
Priority to HU9901351A priority patent/HU221246B1/hu
Priority to NZ307926A priority patent/NZ307926A/en
Priority to HK98119234.9A priority patent/HK1016871B/xx
Priority to AT96915718T priority patent/ATE204180T1/de
Priority to KR1019970708934A priority patent/KR100499648B1/ko
Priority to DK96915718T priority patent/DK0837698T3/da
Priority to BR9608564A priority patent/BR9608564A/pt
Priority to MX9709316A priority patent/MX9709316A/es
Application filed by American Cyanamid Co filed Critical American Cyanamid Co
Priority to EP96915718A priority patent/EP0837698B1/en
Priority to JP9500547A priority patent/JPH11508232A/ja
Priority to DE69614551T priority patent/DE69614551T2/de
Publication of WO1996040261A1 publication Critical patent/WO1996040261A1/en
Priority to BG102100A priority patent/BG63492B1/bg
Priority to NO19975706A priority patent/NO324609B1/no
Anticipated expiration legal-status Critical
Priority to GR20010401797T priority patent/GR3036930T3/el
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • A61K47/6881—Cluster-antibody conjugates, i.e. the modifying agent consists of a plurality of antibodies covalently linked to each other or of different antigen-binding fragments covalently linked to each other
    • 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
    • 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
    • A61K47/6807—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense
    • A61K47/6809—Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to methods for producing monomeric calicheamicin derivative/carrier conjugates.
  • the potent family of antibacterial and antitumor agents known collectively as the calicheamicins or the LL-E33288 complex, are described in U.S. Pat. No..4,970, 198 (1990).
  • the most potent of the agents is designated ⁇ ,', which is herein referenced simply as gamma.
  • These compounds contain a methyltrisulfide that can be reacted with appropriate thiols to form disulfides, at the same time introducing a functional group such as a hydrazide or other functional group that is useful in attaching a calicheamicin derivative to a carrier. Examples of this reaction with the calicheamicins are given in U.S. Pat. No.
  • the amount of calicheamicin loaded on the carrier protein (the drug loading), the amount of aggregate that is formed in the conjugation reaction, and the yield of final purified monomeric conjugate that can be obtained are therefore all related. A compromise must therefore be made between higher drug loadings and the yield of the final monomer by adjusting the amount of the reactive calicheamicin derivative that is added to the conjugation reaction.
  • the tendency for calicheamicin conjugates to aggregate is especially problematic when the conjugation reactions are performed with the linkers described in European Patent Application No. 0689845. In this case, a large percentage of the conjugates produced are in an aggregated form that is quite difficult to purify further for therapeutic administration. For some carrier proteins, conjugates with even modest loadings are virtually impossible to make except on small scale.
  • the calicheamicin derivative/carrier conjugates of the present invention have the formula
  • Pr is a proteinaceous carrier
  • X is a linker that comprises a product of any reactive group that can react with a proteinaceous carrier
  • W is the calicheamicin radical formed by removal of the naturally occuring methyl trisulfide group; and m is a number from 0.5 to 15.
  • a method of the present invention for preparing monomeric calicheamicin derivative/carrier conjugates with higher drug loading/yield and decreased aggregation comprises the steps of:
  • An alternative embodiment of the method of the present invention for preparing monomeric calicheamicin derivative/carrier conjugates with higher drug loading/yield and decreased aggregation comprises the steps of:
  • the conjugates of the present invention include a therapeutic agent derivatized with a linker that includes any reactive group that reacts with a proteinaceous targeting carrier.
  • a linker that includes any reactive group that reacts with a proteinaceous targeting carrier.
  • the use of particular cosolvents and additives induces the monomeric form as opposed to the aggregate form of these conjugates and allows for higher drug loading/yield without excessive aggregation.
  • the monomeric form has therapeutic value.
  • the carriers of the present invention preferably are proteinaceous carriers. Included as carrier molecules are growth factors, antibodies, antibody fragments, and their genetically or enzymatically engineered counterparts, hereinafter referred to singularly or as a group as carriers.
  • the essential property of the carrier is its ability to recognize an antigen or receptor associated with undesired cells. Examples of carriers are given in U.S. Pat. No. 5,053,394, and such carriers are also appropriate in the present invention.
  • Preferred carriers for use in the present invention are human or humanized antibodies.
  • carriers which are exemplified herein are the antibodies P67.6, A33, CT-M-01 (also known as 7F11C7) and the "anti- Tac" antibody of Waldman. These antibodies are used herein in two forms: a murine form, designated by an “m” (e.g., m-P67.6), and a genetically engineered, humanized form, designated by an "h” (e.g., h-P67.6) whenever appropriate.
  • m e.g., m-P67.6
  • h e.g., h-P67.6
  • m-P67.6 is disclosed in I.D. Bernstein et al.. J. Clin. Invest. 79:1153 (1987) and I.D. Bernstein et al., ⁇ Immunol. 122:867-881 (1992) and recognizes the CD33 antigen which is prevalent on certain human myeloid tumors, especially acute non- lymphocytic leukemia (ANLL).
  • ANLL acute non- lymphocytic leukemia
  • Another antibody that can be used is MOPC-
  • the antibody m-CT-M-01 is disclosed in European Patent Application No. 86401482.4/0208615 and recognizes the polyepithelial mucin (PEM) antigen present on many human solid tumors, particularly breast, lung, and ovarian tumors.
  • the humanized version of this antibody, h-CT-M-01 is described in PCT Publication No. WO 93/06231 (1993).
  • the antibody m-A33 is disclosed in U.S. Patent Nos. 5,160,723 and 5,431,897 and is a murine antibody which recognizes a glycoprotein antigen present on colon cancer cells.
  • the humanized version of this antibody, h-A33 is disclosed in PCT Patent Publication No. WO94/13805 (June 23, 1994).
  • Anti-Tac is disclosed in T.A. Waldman et al.. J. Immunol. 126:1393 (1981), and is a murine antibody reactive with the IL-2 receptor that is found on activated and functionally mature T cells, including abnormally activated leukemia cells.
  • the therapeutic agents suitable for use in the present invention are cytotoxic antibiotics that bind to and disrupt DNA.
  • Preferred cytotoxic agents are the calicheamicins which are methyl trisulfide antitumor antibiotics.
  • Examples of calicheamicins suitable for use in the present invention are disclosed, for example, in U.S. Pat. No. 5,053,394. See also, U.S. Patent Nos. 4,671,958; 4,970,198; 5,037,651; and 5,079,233.
  • Preferred calicheamicins are gamma calicheamicin of N-acetyl gamma calicheamicins. The structure of N-acetyl gamma-calicheamicin in a conjugated form is illustrated below.
  • the conjugates of the present invention have the formula
  • Pr is a proteinaceous carrier
  • X is a linker that comprises a product of any reactive group that can react with a proteinaceous carrier
  • W is the calicheamicin radical formed by removal of the naturally occuring methyl trisulfide group; and m is a number from 0.5 to 15.
  • X has the formula Z-Sp wherein:
  • Sp is a straight or branched-chain divalent or trivalent (C,-C 18 ) radical, divalent or trivalent aryl or heteroaryl radical, divalent or trivalent (C 3 -C 18 ) cycloalkyi or heterocycloalkyi radical, divalent or trivalent aryl- or heteroaryl-aryl (C C 18 ) radical, divalent or trivalent cycloalkyi- or heterocycloalkyl-alkyl (C C 18 ) radical or divalent or trivalent (C 2 -C 18 ) unsaturated alkyl radical, wherein heteroaryl is preferably furyl, thienyl, N- methylpyrrolyl, pyridinyl, N-methylimidazolyl, oxazolyl, pyrimidinyl, quinolyl, isoquinolyl, N-methylcarbazoyl, aminocourmarinyl, or phenazinyl and wherein if Sp is a trivalent radical, Sp can be additionally substitute
  • Alk' and Alk 2 are independently a bond or branched or unbranched (C,-C 10 ) alkylene chain;
  • Ar is 1,2-, 1,3-, or 1 ,4-phenylene optionally substituted with one, two, or three groups of (C r C 6 ) alkyl, (C,-C 3 ) alkoxy, (C ⁇ C thioalkoxy, halogen, nitro, -COOR', -CONHR', -0(CH 2 ) n COOR', -S(CH 2 ) n COOR', -O(CH 2 ) n CONHR', or -S(CH 2 ) n CONHR' wherein n and R' are as hereinbefore defined or a 1 ,2-, 1 ,3-, 1,4-, 1 ,5-, 1 ,6-, 1,7-, 1 ,8-, 2,3-, 2,6-, or 2,7-naphthylidene or
  • each naphthylidene or phenothiazine optionally substituted with one, two, three, or four groups of (C,- ⁇ ) alkyl, (C C 5 ) alkoxy, (C r C 4 ) thioalkoxy, halogen, nitro, -COOR', -CONHR', -0(CH 2 ) n COOR', -S(CH 2 ) n COOR', or -S(CH 2 ) ⁇ CONHR' wherein n and R' are as defined above, with the proviso that when Ar is phenothiazine, Sp 1 is a bond only connected to nitrogen;
  • Sp 2 is a bond, -S-, or -0-, with the proviso that when Alk 2 is a bond, Sp 2 is a bond;
  • Z 1 is H, (C C 5 ) alkyl, or phenyl optionally substituted with one, two, or three groups of (C C 5 ) alkyl, alkoxy, (C C 4 ) thioalkoxy, halogen, nitro, -COOR', -CONHR', -0(CH 2 ) n COOR', -S(CH 2 ) n COOR',
  • Sp is a straight or branched-chain divalent or trivalent (0,-C ⁇ ) radical, divalent or trivalent aryl or heteroaryl radical, divalent or trivalent (C 3 -C 18 ) cycloalkyi or heterocycloalkyi radical, divalent or trivalent aryl- or heteroaryl-aryl (C C 1 ⁇ ) radical, divalent or trivalent cycloalkyi- or heterocycloalkyl-alkyl (C C 18 ) radical or divalent or trivalent (C 2 -C 18 ) unsaturated alkyl radical, wherein heteroaryl is preferably furyl, thienyl, N- methylpyrrolyl, pyridinyl, N-methylimidazolyl, oxazolyl, pyrimidinyl, quinolyl, isoquinolyl, N-methylcarbazoyl, aminocourmarinyl, or phenazinyl and wherein if Sp is a trivalent radical, Sp can be additionally substituted
  • Alk 1 is a branched or unbranched (C C 10 ) alkylene chain
  • Sp' is a bond, -S-, -0-, -CONH-, -NHCO-, or -NR' wherein R' is as hereinbefore defined, with the proviso that when Alk 1 is a bond, Sp 1 is a bond;
  • Ar is 1 ,2-, 1 ,3-, or 1 ,4-phenylene optionally substituted with one, two, or three groups of (C r C 6 ) alkyl, alkoxy, (C r C 4 ) thioalkoxy, halogen, nitro, -COOR', -CONHR', -0(CH 2 ) n COOR', -S(CH 2 ) n COOR', -0(CH 2 ) n CONHR', or -S(CH 2 ) ⁇ CONHR' wherein n and R' are as hereinbefore defined, or Ar is a 1,2-, 1,3-, 1 ,4-, 1 ,5-, 1,6-, 1,7-, 1 ,8-, 2,3-, 2,6-, or 2,7- naphthylidene each optionally substituted with one, two, three, or four groups of (C C 6 ) alkyl, (C 1 -C 5 ) alkoxy, (C C
  • Z 1 is (C C 5 ) alkyl, or phenyl optionally substituted with one, two, or three groups of (C ⁇ Cs) alkyl, (C C 4 ) alkoxy, (C ⁇ C thioalkoxy, halogen, nitro, -COOR', -CONHR', -0(CH 2 ) n COOR', -S(CH 2 ) n COOR ⁇
  • Calicheamicin derivatives can, for example, be attached to lysine residues of the antibody. Lysine attachment as disclosed in U.S. Pat.
  • U.S. Pat. No. 5,053,394 also discloses conjugates where a nucleophilic calicheamicin derivative, such as a hydrazide, is reacted with periodate oxidized carbohydrates on an antibody under mildly acidic conditions. This produces a Schiff base or derivative thereof, such as a hydrazone, which can be further reduced with, e.g., cyanoborohydride, if desired, to produce a hydrolytically stable conjugate.
  • a nucleophilic calicheamicin derivative such as a hydrazide
  • European Patent Application No. 0689845 discloses other linkers that can be used with nucleophilic derivatives, particularly hydrazides and related nucleophiles, prepared from the calicheamicins. These linkers are useful in those cases (e.g., P67.6), where better activity is obtained when the linkage formed between the drug and the linker is hydrolyzable. These linkers contain two functional groups. One group typically is a carboxylic acid that is utilized to react with the carrier. The acid functional group.when properly activated, can form an amide linkage with a free amine group of the carrier, such as, for example, the amine in the side chain of a lysine of a monoclonal antibody carrier.
  • the other functional group commonly is a carbonyl group, i.e., an aldehyde or a ketone, which will react with the appropriately modified therapeutic agent.
  • the carbonyl groups can react with a hydrazide group on the drug to form a hydrazone linkage. This linkage is hydrolyzable at the target cell to release the therapeutic agent from the conjugate.
  • a most preferred bifunctional linker for use in the present invention is 4-(4-acetylphenoxy) butanoic acid (AcBut), which results in a preferred product where the conjugate consists of gamma calicheamicin or N-acetyl gamma calicheamicin functionalized by reacting with the hydrazide of 3-mercapto-3-methyl butanoic acid, the linker 4-(4-acetylphenoxy)butanoic acid (AcBut), and a human or humanized monoclonal antibody targeting carrier.
  • AcBut 4-(4-acetylphenoxy) butanoic acid
  • humanized carriers including, but not limited to, proteins such as human or humanized monoclonal antibodies that are used to target the cytotoxic therapeutic agents herein, such as, for example, P67.6 and the other humanized monoclonal antibodies disclosed herein, use of a non- nucleophilic, protein-compatible, buffered solution containing (i) propylene glycol (PG) as a cosolvent and (ii) an additive comprising at least one C 6 -
  • C 18 carboxylic acid was found to produce monomeric calicheamicin derivative/carrier conjugates with higher drug loading/yield and decreased aggregation having excellent activity.
  • Preferred acids are C 7 to C 12 acids, and the most preferred acid is octanoic (caprylic) acid (CA).
  • Preferred buffered solutions for conjugates made from OSu esters or other comparably activated esters are phosphate-buffered saline (PBS) or N-2- hydroxyethyl piperazine-N'-2-ethane sulfonic acid (Hepes buffer), while preferred buffered solutions for conjugates made from the oxidized carbohydrates of antibodies is sodium acetate.
  • PBS phosphate-buffered saline
  • Hepes buffer N-2- hydroxyethyl piperazine-N'-2-ethane sulfonic acid
  • preferred buffered solutions for conjugates made from the oxidized carbohydrates of antibodies is sodium acetate.
  • Acceptable buffers for other types of conjugates can be readily determined by those who are skilled in the art.
  • the use of a non- nucleophilic, protein-compatible, buffered solution containing t-butanol without an additive was also found to produce monomeric calicheamicin derivative/carrier conjugates with higher drug loading/yield and decreased aggregation.
  • the amount of cosolvent used is a monomeric conjugating effective amount and can be determined by those of ordinary skill in the art without undue experimentation.
  • the amount of additive is a monomeric conjugation enhancing effective amount. This amount can also be determined by one of ordinary skill in the art without undue experimentation.
  • PG propylene glycol
  • Some or all of the PG cosolvent is used to transfer the drug into the conjugation mixture. When the cosolvent used for drug transfer amounts to 10% or less of the total volume of the conjugation mixture, it can optionally be substituted by ethanol or DMSO.
  • the concentration of the C 6 - C 18 carboxylic acid, preferably caprylic acid can be increased to 150-300 mM and the cosolvent dropped to 1-10% propylene glycol, ethanol, or DMSO, and is preferably
  • t-butanol at concentrations ranging from about 10% to about 25%, preferably about 15%, by volume of the total solution may be added to the conjugation reaction to produce monomeric calicheamicin derivative/carrier conjugates with higher drug loading/yield and decreased aggregation.
  • the concentration of MoAb ranges from about 1 to about 15 mg/ml and the concentration of the drug, e.g., AcBut calicheamicin, ranges from about 0.025 to about 1 mg/ml.
  • the reactions are performed in PBS or acetate buffer at a pH of from about 4.0 to about 8.5, depending on the type of conjugate being made, at a temperature ranging from about room temperature (25° C) to about 37° C for times ranging from about 15 minutes to about 24 hours.
  • the conjugates may be recovered and purified by conventional methods, for example, HPLC, FPLC or SEPHACRYL S-200TM.
  • the purified conjugates are monomeric and contain from about 2 to about 6 moles/mole drug/MoAb.
  • the addition of cosolvent and/or the additive may alter the pH of the buffered solution so that it may be necessary to adjust the pH of the solution to the preferred pH range of about 4.0 to 8.5.
  • the pH of the buffered solution containing the cosolvent and the additive will be about 7.0 to 8.5 for conjugates made from OSu esters, or about 4.0 to 6.5 for conjugates made from the oxidized carbohydrates of the antibody.
  • the pH of the buffered solution containing the cosolvent and the additive will be about 7.7 for conjugates made from OSu esters, or about 5.5 for conjugates made from the oxidized carbohydrates of the antibody.
  • Acceptable pH ranges for other types of conjugates can be readily determined by those who are skilled in the art.
  • the first set of experiments were performed with N-acetyl gamma calicheamicin functionalized by reacting with the hydrazide of 3- mercapto-3-methyl butanoic acid attached to the linker 4-(4- acetylphenoxy)butanoic acid and activated as the OSu ester (herein referred to as AcBut calicheamicin) on both murine and human P67.6 with variations in DMF concentrations, drug/protein ratio, and buffer.
  • IPA IPA
  • 25% t-butanol 25% PG + 80 mM CA. All were done with 3.25 mg/mL protein (final) in PBS, pH 7.4, and 6 moles drug per mole MoAb. All were compared to a control conjugation performed in 25% DMF while all the test solutions contained ⁇ 5% DMF from the drug stock. Conjugation was also done with 4 M/M drug in 25% PG or 25% DMF as control. All samples were incubated at room temperature overnight, exchanged into PBS on PD10 columns, and analyzed by spectrophotometry for protein recovery and drug loading. Samples were further analyzed by HPLC on ZorbaxTM and SuperoseTM. Following the conjugation reaction, the conjugates were purified on FPLC SuperoseTM. Results: All of these additives seemed beneficial except glycerol (low loading). PG + CA seemed best in terms of conjugate yield, drug loading and minimizing aggregate.
  • CA were incompatible at these concentrations, while IPA was not as good as PG in improving yield and decreasing aggregate.
  • CT-M-01 monoclonal antibody in the presence of 25% propylene glycol (PG) and 80% caprylic acid. The reaction was performed overnight
  • Example 9 AcBut-calicheamicin was conjugated to 36.6 mg hCT-M-01 monoclonal antibody in the presence of 30% PG and 60 mM CA. The reaction was performed for 2 hours at about 25°C. The product was analyzed by HPLC.
  • AcBut-calicheamicin was conjugated to 1 mg humanized A33 MoAb in the presence of 30% PG and 60 mM CA.
  • the pH was adjusted by addition of -10 mL NaOH/mL of solution to obtain a pH of 7.7-7.8.
  • the drug was then added and the solution mixed vigorously.
  • the solution was incubated at 25°C with shaking for 3 hours followed by filtration through Millex HV filters to remove insoluble material.
  • the conjugate was then purified by gel filtration on SEPHACRYL S-200TM in PBS (pH 7.4) using no more than a -1% load or, for small conjugations ⁇ 0.5 mL, SuperoseTM 12 FPLC in PBS was utilized.
  • Final monomeric ( ⁇ 4% dimer) conjugate was produced in >60% protein yield with a drug loading of >2.5 moles drug/mole protein.
  • Protein yields were modest, ranging from 20 to 40%.
  • final loading on monomer was only 1.1-1.3 M/M.
  • the anti-Tac conjugate, with a loading of 0.7 m/M, was reconjugated in the presence of 20% t-BuOH since that was the best backup additive. This increased loading to 2.0 M/M but in only 23% yield.
  • MOPC-21 was oxidized in pH 5.5 acetate buffer with 15 mM Nal0 4 at ambient temperature for 45 minutes. The buffered was then exchanged for fresh acetate buffer to remove the spent oxidation reagents. A portion of this oxidized antibody was treated with the disulfide resulting from the reaction of N-acetyl gamma-calicheamicin with the hydrazide of 3- mercapto-3-methyl butanoic acid (GAD) in the presence of 15% DMF. A second portion was treated with the same concentration of GAD in the presence of 5% DMF and 15% tBuOH. Both reactions were allowed to proceed at ambient temperature for 17 hours. Each reaction then had the buffer exchanged for pH 7.4 PBS.
  • GAD 3- mercapto-3-methyl butanoic acid

Landscapes

  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
PCT/US1996/006738 1995-06-07 1996-05-10 Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates Ceased WO1996040261A1 (en)

Priority Applications (15)

Application Number Priority Date Filing Date Title
MX9709316A MX9709316A (es) 1995-06-07 1996-05-10 Metodos para la preparacion de conjugados monomericos de derivado de caliqueamicina/portador.
NZ307926A NZ307926A (en) 1995-06-07 1996-05-10 Methods for the preparation of monomeric calicheamicin derivative/carrier conjuates
EP96915718A EP0837698B1 (en) 1995-06-07 1996-05-10 Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
AT96915718T ATE204180T1 (de) 1995-06-07 1996-05-10 Verfahren zur herstellung von monomeren calicheamicinderivaten/trägerkonjugaten
KR1019970708934A KR100499648B1 (ko) 1995-06-07 1996-05-10 단량체칼리케아미신유도체/캐리어공액체의제조방법
DK96915718T DK0837698T3 (da) 1995-06-07 1996-05-10 Fremgangsmåder til fremstilling af monomere calicheamicin-derivat/bærer-konjugater
BR9608564A BR9608564A (pt) 1995-06-07 1996-05-10 Processo para a preparação de conjugados de derivado de caliqueamicina/veículo monoméricos
AU57423/96A AU703862B2 (en) 1995-06-07 1996-05-10 Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
HK98119234.9A HK1016871B (en) 1995-06-07 1996-05-10 Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
HU9901351A HU221246B1 (en) 1995-06-07 1996-05-10 Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
JP9500547A JPH11508232A (ja) 1995-06-07 1996-05-10 モノマー性カリキアミシン誘導体／キャリアー複合体の調製方法
DE69614551T DE69614551T2 (de) 1995-06-07 1996-05-10 Verfahren zur herstellung von monomeren calicheamicinderivaten/trägerkonjugaten
BG102100A BG63492B1 (bg) 1995-06-07 1997-12-03 Методи за получаване на мономерни конюгати калихеамициново производно/носител
NO19975706A NO324609B1 (no) 1995-06-07 1997-12-05 Fremgangsmater for fremstilling av monomere calicheamicin-derivat/baerer-konjugater
GR20010401797T GR3036930T3 (en) 1995-06-07 2001-10-18 Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US08/475,005 1995-06-07
US08/475,005 US5712374A (en) 1995-06-07 1995-06-07 Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates

Publications (1)

Publication Number Publication Date
WO1996040261A1 true WO1996040261A1 (en) 1996-12-19

Family

ID=23885856

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/006738 Ceased WO1996040261A1 (en) 1995-06-07 1996-05-10 Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates

Country Status (27)

Country Link
US (1) US5712374A (enExample)
EP (1) EP0837698B1 (enExample)
JP (2) JPH11508232A (enExample)
KR (1) KR100499648B1 (enExample)
CN (1) CN1094063C (enExample)
AR (1) AR002360A1 (enExample)
AT (1) ATE204180T1 (enExample)
AU (1) AU703862B2 (enExample)
BG (1) BG63492B1 (enExample)
BR (1) BR9608564A (enExample)
CA (1) CA2223329A1 (enExample)
CY (1) CY2355B1 (enExample)
CZ (1) CZ298024B6 (enExample)
DE (1) DE69614551T2 (enExample)
DK (1) DK0837698T3 (enExample)
ES (1) ES2160818T3 (enExample)
GR (1) GR3036930T3 (enExample)
HU (1) HU221246B1 (enExample)
IL (1) IL118565A (enExample)
IN (1) IN182139B (enExample)
MX (1) MX9709316A (enExample)
NO (1) NO324609B1 (enExample)
NZ (1) NZ307926A (enExample)
PT (1) PT837698E (enExample)
TW (1) TW419377B (enExample)
WO (1) WO1996040261A1 (enExample)
ZA (1) ZA964614B (enExample)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005089809A3 (en) * 2004-03-15 2006-05-04 Wyeth Corp Calicheamicin conjugation by antibody deglycosylation
US8153768B2 (en) 2002-05-02 2012-04-10 Wyeth Holdings Corporation Calicheamicin derivative-carrier conjugates
KR101454489B1 (ko) 2006-02-21 2014-10-27 와이어쓰 엘엘씨 칼리케아미신 유도체의 수렴형 합성 방법

Families Citing this family (632)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6914130B2 (en) * 1998-06-17 2005-07-05 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
US20050159588A1 (en) * 1999-06-02 2005-07-21 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
KR100850389B1 (ko) 1999-06-25 2008-08-04 제넨테크, 인크. 인간화 항-ＥｒｂＢ2 항체 및 항-ＥｒｂＢ2 항체를 사용한치료 방법
MXPA02010011A (es) 2000-04-11 2003-04-25 Genentech Inc Anticuerpos multivalentes y usos para los mismos.
CN1463270A (zh) * 2001-05-31 2003-12-24 梅达莱克斯公司 细胞毒素、其有用的前体药物、连接基团和稳定剂
IL158969A0 (en) 2001-06-01 2004-05-12 Cornell Res Foundation Inc Modified antibodies to prostate-specific membrane antigen and uses thereof
US20070160576A1 (en) 2001-06-05 2007-07-12 Genentech, Inc. IL-17A/F heterologous polypeptides and therapeutic uses thereof
US7803915B2 (en) * 2001-06-20 2010-09-28 Genentech, Inc. Antibody compositions for the diagnosis and treatment of tumor
US20050107595A1 (en) * 2001-06-20 2005-05-19 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
KR100628425B1 (ko) 2001-06-20 2006-09-28 제넨테크, 인크. 종양의 진단 및 치료를 위한 방법 및 이를 위한 조성물
US20060073141A1 (en) * 2001-06-28 2006-04-06 Domantis Limited Compositions and methods for treating inflammatory disorders
JP2005536439A (ja) 2001-09-18 2005-12-02 ジェネンテック・インコーポレーテッド 腫瘍の診断及び治療のための組成物と方法
NZ533933A (en) 2002-01-02 2008-06-30 Genentech Inc Compositions and methods for the diagnosis and treatment of glioma tumor
US20040132101A1 (en) 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
US8093357B2 (en) * 2002-03-01 2012-01-10 Xencor, Inc. Optimized Fc variants and methods for their generation
US20090042291A1 (en) * 2002-03-01 2009-02-12 Xencor, Inc. Optimized Fc variants
US20100311954A1 (en) * 2002-03-01 2010-12-09 Xencor, Inc. Optimized Proteins that Target Ep-CAM
CA2481507A1 (en) 2002-04-16 2003-10-30 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
AU2012244218C1 (en) * 2002-05-02 2016-12-15 Wyeth Holdings Llc. Calicheamicin derivative-carrier conjugates
AU2015246156B2 (en) * 2002-05-02 2017-06-29 Wyeth Holdings Llc. Calicheamicin derivative-carrier conjugates
GB0210121D0 (en) * 2002-05-02 2002-06-12 Celltech R&D Ltd Biological products
WO2004008099A2 (en) 2002-07-15 2004-01-22 Genentech, Inc. METHODS FOR IDENTIFYING TUMORS THAT ARE RESPONSIVE TO TREATMENT WITH ANTI-ErbB2 ANTIBODIES
EP2298805A3 (en) 2002-09-27 2011-04-13 Xencor, Inc. Optimized Fc variants and methods for their generation
US20090010920A1 (en) * 2003-03-03 2009-01-08 Xencor, Inc. Fc Variants Having Decreased Affinity for FcyRIIb
US8388955B2 (en) 2003-03-03 2013-03-05 Xencor, Inc. Fc variants
AU2004259638C1 (en) 2003-07-08 2018-12-20 Novartis Pharma Ag IL-17 A/F heterologous polypeptides and therapeutic uses thereof
AU2004261980A1 (en) * 2003-08-01 2005-02-10 Genentech, Inc. Antibody CDR polypeptide sequences with restricted diversity
US8101720B2 (en) * 2004-10-21 2012-01-24 Xencor, Inc. Immunoglobulin insertions, deletions and substitutions
US9714282B2 (en) 2003-09-26 2017-07-25 Xencor, Inc. Optimized Fc variants and methods for their generation
ATE453405T1 (de) 2003-11-17 2010-01-15 Genentech Inc Zusammensetzungen und verfahren zur behandlung von tumoren hämatopoetischen ursprungs
CN1922210A (zh) 2003-12-19 2007-02-28 健泰科生物技术公司 可用作治疗剂的单价抗体片段
MXPA06011199A (es) 2004-03-31 2007-04-16 Genentech Inc Anticuerpos anti-tgf-beta humanizados.
MXPA06013413A (es) * 2004-05-19 2007-01-23 Medarex Inc Enlazadores quimicos y conjugados de los mismos.
RU2402548C2 (ru) * 2004-05-19 2010-10-27 Медарекс, Инк. Химические линкеры и их конъюгаты
JP2008505174A (ja) 2004-07-15 2008-02-21 ゼンコー・インコーポレイテッド 最適化Ｆｃ変異体
WO2006014729A2 (en) 2004-07-20 2006-02-09 Genentech, Inc. Inhibitors of angiopoietin-like 4 protein, combinations, and their use
KR101222254B1 (ko) 2004-07-26 2013-01-16 제넨테크, 인크. 간세포 성장 인자 활성화를 조정하기 위한 조성물 및 방법
CA2486285C (en) * 2004-08-30 2017-03-07 Viktor S. Goldmakher Immunoconjugates targeting syndecan-1 expressing cells and use thereof
EP1784426B1 (en) * 2004-09-03 2011-11-23 Genentech, Inc. Humanized anti-beta7 antagonists and uses therefor
CN101065151B (zh) 2004-09-23 2014-12-10 健泰科生物技术公司 半胱氨酸改造的抗体和偶联物
JO3000B1 (ar) 2004-10-20 2016-09-05 Genentech Inc مركبات أجسام مضادة .
EP2325206B1 (en) 2004-11-12 2014-03-19 Xencor, Inc. Fc variants with altered binding to fcrn
US8546543B2 (en) 2004-11-12 2013-10-01 Xencor, Inc. Fc variants that extend antibody half-life
US8367805B2 (en) 2004-11-12 2013-02-05 Xencor, Inc. Fc variants with altered binding to FcRn
US20070135620A1 (en) * 2004-11-12 2007-06-14 Xencor, Inc. Fc variants with altered binding to FcRn
US8802820B2 (en) * 2004-11-12 2014-08-12 Xencor, Inc. Fc variants with altered binding to FcRn
DK1841793T3 (da) 2005-01-07 2010-07-19 Diadexus Inc Ovr110-antistofsammensætninger og fremgangsmåder til anvendelse deraf
TWI441646B (zh) 2005-01-21 2014-06-21 Genentech Inc 帕妥珠單抗(pertuzumab)用於製備治療人類病患癌症之藥物的用途
DK1851250T3 (da) * 2005-02-18 2012-07-09 Medarex Inc Humant monoklonalt antistof mod prostataspecifikt membranantigen (psma)
CA2596133C (en) 2005-02-23 2016-11-15 Genentech, Inc. Extending time to disease progression or survival in cancer patients
TW200642695A (en) * 2005-03-08 2006-12-16 Genentech Inc Methods for identifying tumors responsive to treatment with her dimerization inhibitors (HDIs)
EP2384767B1 (en) 2005-03-24 2016-03-09 Millennium Pharmaceuticals, Inc. Antibodies that bind OV064 and methods of use therefor
AU2006235276A1 (en) 2005-04-07 2006-10-19 Novartis Vaccines And Diagnostics Inc. CACNA1E in cancer diagnosis, detection and treatment
CA2604844A1 (en) 2005-04-07 2006-10-19 Novartis Vaccines And Diagnostics, Inc. Cancer-related genes
US7714016B2 (en) * 2005-04-08 2010-05-11 Medarex, Inc. Cytotoxic compounds and conjugates with cleavable substrates
CA2610709A1 (en) 2005-06-06 2006-12-14 Genentech, Inc. Transgenic models for different genes and their use for gene characterization
US20070003559A1 (en) * 2005-07-01 2007-01-04 Wyeth Methods of determining pharmacokinetics of targeted therapies
CA2652434A1 (en) 2005-07-08 2007-01-18 Xencor, Inc. Optimized proteins that target ep-cam
JP2009504183A (ja) 2005-08-15 2009-02-05 ジェネンテック・インコーポレーテッド 遺伝子破壊、それに関連する組成物および方法
WO2007041364A2 (en) 2005-09-30 2007-04-12 Government Of The United States Of America, As Represented By The Secretary Conjugates for modulating the immune tolerance
DK1931709T3 (en) 2005-10-03 2017-03-13 Xencor Inc FC VARIETIES WITH OPTIMIZED FC RECEPTOR BINDING PROPERTIES
ES2375843T3 (es) 2005-10-26 2012-03-06 Medarex, Inc. Procedimientos y compuestos para la preparación de an�?logos de cc-1065.
WO2007056441A2 (en) 2005-11-07 2007-05-18 Genentech, Inc. Binding polypeptides with diversified and consensus vh/vl hypervariable sequences
WO2007059404A2 (en) 2005-11-10 2007-05-24 Medarex, Inc. Duocarmycin derivatives as novel cytotoxic compounds and conjugates
US20090293137A1 (en) 2005-11-21 2009-11-26 Genentech, Inc. Novel Gene Disruptions, Compositions and Methods Relating Thereto
US8957187B2 (en) * 2005-12-02 2015-02-17 Genentech, Inc. Binding polypeptides and uses thereof
CN105859886A (zh) 2005-12-02 2016-08-17 健泰科生物技术公司 牵涉与il-22和il-22r结合的抗体的组合物和方法
WO2007064919A2 (en) * 2005-12-02 2007-06-07 Genentech, Inc. Binding polypeptides with restricted diversity sequences
WO2007067602A1 (en) * 2005-12-06 2007-06-14 Wyeth Interleukin-11 compositions and methods of use
EP1973948B1 (en) 2005-12-15 2015-02-11 Genentech, Inc. Methods and compositions for targeting polyubiquitin
RU2450020C2 (ru) 2006-01-05 2012-05-10 Дженентек, Инк. АНТИТЕЛА ПРОТИВ EphB4 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
ZA200807714B (en) 2006-02-17 2010-01-27 Genentech Inc Gene disruptions, compositions and methods relating thereto
EP2946786A1 (en) 2006-03-08 2015-11-25 Wake Forest University Health Sciences Soluble monomeric Ephrin A1
AU2007226696C1 (en) 2006-03-10 2016-02-04 Wyeth Llc Anti-5T4 antibodies and uses thereof
AR059851A1 (es) 2006-03-16 2008-04-30 Genentech Inc Anticuerpos de la egfl7 y metodos de uso
WO2007109376A2 (en) 2006-03-23 2007-09-27 Novartis Ag Anti-tumor cell antigen antibody therapeutics
EP2007428A2 (en) 2006-04-05 2008-12-31 Genentech, Inc. Method for using boc/cdo to modulate hedgehog signaling
BRPI0710616A2 (pt) 2006-04-13 2011-08-16 Novartis Vaccines & Diagnostic métodos para tratar, diagnosticar ou detectar cáncer
JP2009536022A (ja) 2006-04-19 2009-10-08 ジェネンテック・インコーポレーテッド 新規の遺伝子破壊、それに関連する組成物および方法
HRP20140172T1 (hr) 2006-05-30 2014-03-28 Genentech, Inc. Protutijela i imunokonjugati kao i njihove uporabe
RS53263B (sr) 2006-08-14 2014-08-29 Xencor Inc. Optimizovana antitela usmerena na cd19
US20100008910A1 (en) 2006-09-12 2010-01-14 John Chant Methods and compositions for the diagnosis and treatment of cancer
CA2667019C (en) 2006-10-27 2016-03-29 Genentech, Inc. Antibodies and immunoconjugates and uses therefor
JP5391073B2 (ja) 2006-11-27 2014-01-15 ディアデクサス インコーポレーテッド Ｏｖｒ１１０抗体組成物および使用方法
TWI412367B (zh) 2006-12-28 2013-10-21 Medarex Llc 化學鏈接劑與可裂解基質以及其之綴合物
PE20081760A1 (es) 2007-02-09 2009-01-01 Genentech Inc Anticuerpos anti-robo4 y sus usos
CN101616911A (zh) 2007-02-21 2009-12-30 梅达莱克斯公司 具有单个氨基酸的化学连接物及其偶联物
PL2132573T3 (pl) * 2007-03-02 2014-09-30 Genentech Inc Prognozowanie odpowiedzi na inhibitor dimeryzacji HER oparte na niskiej ekspresji HER3
JP2010521180A (ja) 2007-03-14 2010-06-24 ノバルティス アーゲー 癌を処置、診断または検出するためのａｐｃｄｄ１阻害剤
US7960139B2 (en) 2007-03-23 2011-06-14 Academia Sinica Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells
LT2176298T (lt) 2007-05-30 2018-04-10 Xencor, Inc. Būdai ir kompozicijos, skirti cd32b ekspresuojančių ląstelių slopinimui
PE20090309A1 (es) * 2007-06-04 2009-04-18 Wyeth Corp Conjugado portador-caliqueamicina y un metodo de deteccion de caliqueamicina
CL2008002085A1 (es) 2007-07-16 2008-11-21 Genentech Inc Anticuerpo humanizado anti-cd79b/igbeta/b29; polinucleotido codificacnte, vector, celula huesped; metodo de fabricacion; inmunoconjugado; composicion farmaceutica; uso para tratar cancer; metodo in vitro para determinar presencia de cd79b, oinhibir crecimiento de celulas quqe expresa cd79b; ensayo in vitro para detectar celulas b
EP2641618A3 (en) 2007-07-16 2013-10-23 Genentech, Inc. Humanized anti-CD79B antibodies and immunoconjugates and methods of use
KR102339457B1 (ko) 2007-09-26 2021-12-14 추가이 세이야쿠 가부시키가이샤 항체 정상영역 개변체
AU2008321016B2 (en) 2007-11-12 2013-03-28 Theraclone Sciences, Inc. Compositions and methods for the therapy and diagnosis of influenza
US20110033476A1 (en) * 2007-11-12 2011-02-10 Theraclone Sciences Inc. Compositions and methods for the therapy and diagnosis of influenza
TWI468417B (zh) 2007-11-30 2015-01-11 Genentech Inc 抗－ｖｅｇｆ抗體
EP2238169A1 (en) * 2007-12-26 2010-10-13 Biotest AG Method of decreasing cytotoxic side-effects and improving efficacy of immunoconjugates
BRPI0821417A2 (pt) * 2007-12-26 2015-06-16 Biotest Ag Método para diminuir a adesão de células de estroma a células tumorais que expressam cd138 em células tumorais de um indivíduo em necessidade do mesmo
KR101616758B1 (ko) 2007-12-26 2016-04-29 젠코어 인코포레이티드 ＦｃＲｎ에 대한 변경된 결합성을 갖는 Ｆｃ 변이체
SI2242772T1 (sl) * 2007-12-26 2015-03-31 Biotest Ag Imunokonjugati, ki ciljajo v CD138, in njihova uporaba
US9221914B2 (en) 2007-12-26 2015-12-29 Biotest Ag Agents targeting CD138 and uses thereof
TWI472339B (zh) 2008-01-30 2015-02-11 Genentech Inc 包含結合至ｈｅｒ２結構域ii之抗體及其酸性變異體的組合物
CN104650230A (zh) 2008-01-31 2015-05-27 健泰科生物技术公司 抗cd79b抗体和免疫偶联物及使用方法
US12492253B1 (en) 2008-02-25 2025-12-09 Xencor, Inc. Anti-human C5 antibodies
WO2009114560A2 (en) 2008-03-10 2009-09-17 Spaltudaq Corporation Compositions and methods for the therapy and diagnosis of cytomegalovirus
EP2271770B1 (en) * 2008-03-31 2018-08-22 Genentech, Inc. Compositions and methods for treating and diagnosing asthma
EP3605088A1 (en) 2008-04-09 2020-02-05 Genentech, Inc. Compositions and methods for the treatment of immune related diseases
KR101361905B1 (ko) * 2008-05-16 2014-02-21 제넨테크, 인크. 베타7 인테그린 길항제를 이용한 위장관 염증 장애의 치료를 평가하기 위한 바이오마커의 용도
JP5986745B2 (ja) 2008-07-15 2016-09-06 アカデミア シニカＡｃａｄｅｍｉａ Ｓｉｎｉｃａ Ｐｔｆｅ様のアルミニウム・コート・ガラススライド上のグリカンアレイおよび関連する方法
AR073717A1 (es) 2008-10-01 2010-11-24 Genentech Inc Anticuerpos anti-notch2 de murino y humano, y metodos de uso
KR20110101212A (ko) 2008-12-17 2011-09-15 제넨테크, 인크. Ｃ형 간염 바이러스 조합 요법
SG172789A1 (en) 2009-02-11 2011-08-29 Novozymes Biopharma Dk As Albumin variants and conjugates
SI3260136T1 (sl) 2009-03-17 2021-05-31 Theraclone Sciences, Inc. Humani imunodeficientni virus (HIV)-nevtralizirajoča protitelesa
MA33198B1 (fr) 2009-03-20 2012-04-02 Genentech Inc Anticorps anti-her di-spécifiques
PE20120553A1 (es) 2009-03-25 2012-05-18 Genentech Inc Anticuerpos anti-fgfr3
MA33210B1 (fr) 2009-03-25 2012-04-02 Genentech Inc Nouveaux anticorps anti-a5b1 et leurs utilisations
EP2414399A1 (en) 2009-04-01 2012-02-08 F. Hoffmann-La Roche AG Anti-fcrh5 antibodies and immunoconjugates and methods of use
CN102369215B (zh) 2009-04-02 2015-01-21 罗切格利卡特公司 包含全长抗体和单链Fab片段的多特异性抗体
EP2918602A1 (en) 2009-04-16 2015-09-16 AbbVie Biotherapeutics Inc. Anti-TNF-alpha antibodies and their uses
US9296785B2 (en) 2009-04-17 2016-03-29 Wake Forest University Health Sciences IL-13 receptor binding peptides
SG175305A1 (en) * 2009-04-23 2011-11-28 Theraclone Sciences Inc Granulocyte-macrophage colony-stimulating factor (gm-csf) neutralizing antibodies
NZ621170A (en) 2009-05-13 2015-08-28 Genzyme Corp Anti-human cd52 immunoglobulins
CA2762302A1 (en) 2009-05-20 2010-11-25 Theraclone Sciences, Inc. Compositions and methods for the therapy and diagnosis of influenza
BRPI1013016A2 (pt) 2009-06-04 2016-03-29 Massachusetts Inst Technology "métodos para identificação de locais para conjugação de igg"
BRPI1012321A8 (pt) 2009-06-17 2016-09-27 Abbott Biotherapeutics Corp Anticorpos anti-vegf e seus usos
AU2010278844A1 (en) 2009-07-31 2012-02-09 Genentech, Inc. Inhibition of tumor metastasis using Bv8- or G-CSF-antagonists
US9321823B2 (en) 2009-09-02 2016-04-26 Genentech, Inc. Mutant smoothened and methods of using the same
US9493578B2 (en) 2009-09-02 2016-11-15 Xencor, Inc. Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens
JP6091894B2 (ja) 2009-09-16 2017-03-15 ジェネンテック， インコーポレイテッド コイルドコイルおよび／またはテザー含有タンパク質複合体およびその使用
DK2488873T3 (en) 2009-10-16 2015-11-09 Novartis Ag Biomarkers for pharmacodynamic tumor responses
EP2491058A1 (en) * 2009-10-19 2012-08-29 F. Hoffmann-La Roche AG Modulators of hepatocyte growth factor activator
KR20120105447A (ko) 2009-10-22 2012-09-25 제넨테크, 인크. 항-헵신 항체 및 그의 사용 방법
CA2778442A1 (en) 2009-10-22 2011-04-28 Genentech, Inc. Methods and compositions for modulating hepsin activation of macrophage-stimulating protein
WO2011056494A1 (en) 2009-10-26 2011-05-12 Genentech, Inc. Activin receptor-like kinase-1 antagonist and vegfr3 antagonist combinations
WO2011056502A1 (en) 2009-10-26 2011-05-12 Genentech, Inc. Bone morphogenetic protein receptor type ii compositions and methods of use
WO2011056497A1 (en) 2009-10-26 2011-05-12 Genentech, Inc. Activin receptor type iib compositions and methods of use
CN102753580A (zh) 2009-10-28 2012-10-24 亚培生物医疗股份有限公司 抗egfr抗体及其用途
RU2607374C2 (ru) 2009-10-30 2017-01-10 Новозаймс Байофарма Дк А/С Варианты альбумина
MX2012005168A (es) 2009-11-05 2012-06-08 Genentech Inc Metodos y composicion para secrecion de polipeptidos heterologos.
RU2015132142A (ru) 2009-11-30 2015-12-20 Дженентек, Инк. Композиции и способы для диагностики и лечения опухоли
US11377485B2 (en) 2009-12-02 2022-07-05 Academia Sinica Methods for modifying human antibodies by glycan engineering
US10087236B2 (en) 2009-12-02 2018-10-02 Academia Sinica Methods for modifying human antibodies by glycan engineering
CN102770456B (zh) 2009-12-04 2018-04-06 弗·哈夫曼-拉罗切有限公司 多特异性抗体、抗体类似物、组合物和方法
PT2949670T (pt) 2009-12-10 2019-05-20 Hoffmann La Roche Anticorpos que se ligam preferencialmente ao domínio extracelular 4 do csf1r e respetiva utilização
US8486397B2 (en) 2009-12-11 2013-07-16 Genentech, Inc. Anti-VEGF-C antibodies and methods using same
EP2513148B1 (en) 2009-12-16 2016-08-31 AbbVie Biotherapeutics Inc. Anti-her2 antibodies and their uses
US8771685B2 (en) 2009-12-23 2014-07-08 F. Hoffmann-La Roche Ag Anti-BV8 antibodies and uses thereof
WO2011089211A1 (en) 2010-01-22 2011-07-28 Synimmune Gmbh Anti-cd133 antibodies and methods of using the same
JP5981853B2 (ja) 2010-02-18 2016-08-31 ジェネンテック， インコーポレイテッド ニューレグリンアンタゴニスト及び癌の治療におけるそれらの使用
KR20130004579A (ko) 2010-02-23 2013-01-11 제넨테크, 인크. 종양의 진단 및 치료를 위한 조성물 및 방법
CA2789071C (en) 2010-03-05 2018-03-27 F. Hoffmann-La Roche Ag Antibodies against human csf-1r and uses thereof
WO2011107553A1 (en) 2010-03-05 2011-09-09 F. Hoffmann-La Roche Ag Antibodies against human csf-1r and uses thereof
TW201134481A (en) 2010-03-12 2011-10-16 Abbott Biotherapeutics Corp CTLA4 proteins and their uses
KR101899835B1 (ko) 2010-03-24 2018-09-19 제넨테크, 인크. 항-ｌｒｐ６ 항체
TW201138821A (en) 2010-03-26 2011-11-16 Roche Glycart Ag Bispecific antibodies
US10233228B2 (en) 2010-04-09 2019-03-19 Albumedix Ltd Albumin derivatives and variants
WO2011130332A1 (en) 2010-04-12 2011-10-20 Academia Sinica Glycan arrays for high throughput screening of viruses
KR101860963B1 (ko) 2010-04-23 2018-05-24 제넨테크, 인크. 이종다량체 단백질의 생산
MA34291B1 (fr) 2010-05-03 2013-06-01 Genentech Inc Compositions et méthodes de diagnostic et de traitement d'une tumeur
WO2011146568A1 (en) 2010-05-19 2011-11-24 Genentech, Inc. Predicting response to a her inhibitor
CA2799915C (en) 2010-05-25 2023-09-26 Genentech, Inc. Methods of purifying polypeptides
CN103119442A (zh) 2010-06-03 2013-05-22 霍夫曼-拉罗奇有限公司 抗体和免疫偶联物的免疫peg成像及其用途
WO2011156328A1 (en) 2010-06-08 2011-12-15 Genentech, Inc. Cysteine engineered antibodies and conjugates
KR101885388B1 (ko) 2010-06-18 2018-08-03 제넨테크, 인크. 항-Ａｘｌ 항체 및 사용 방법
WO2011161119A1 (en) 2010-06-22 2011-12-29 F. Hoffmann-La Roche Ag Antibodies against insulin-like growth factor i receptor and uses thereof
WO2011161189A1 (en) 2010-06-24 2011-12-29 F. Hoffmann-La Roche Ag Anti-hepsin antibodies and methods of use
EP3029066B1 (en) 2010-07-29 2019-02-20 Xencor, Inc. Antibodies with modified isoelectric points
RU2013106216A (ru) 2010-08-03 2014-09-10 Ф. Хоффманн-Ля Рош Аг Биомаркеры хронической лимфоцитарной лейкемии
EP2603237A4 (en) 2010-08-12 2014-05-21 Theraclone Sciences Inc ANTI-HEMAGGLUTININE ANTIBODY COMPOSITIONS AND METHOD FOR THEIR USE
RU2013110844A (ru) 2010-08-13 2014-09-20 Дженентек, Инк. АНТИТЕЛА ПРОТИВ IL-1β И IL-18, ИСПОЛЬЗУЕМЫЕ ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ
RU2584597C2 (ru) 2010-08-13 2016-05-20 Рош Гликарт Аг Антитела против а2 тенасцина с и способы их применения
ES2655616T3 (es) 2010-08-13 2018-02-20 Roche Glycart Ag Anticuerpos anti-FAP y procedimientos de uso
WO2012025530A1 (en) 2010-08-24 2012-03-01 F. Hoffmann-La Roche Ag Bispecific antibodies comprising a disulfide stabilized - fv fragment
PL3556396T3 (pl) 2010-08-31 2022-09-12 Theraclone Sciences, Inc. Przeciwciała neutralizujące ludzki wirus niedoboru odporności (hiv)
AU2011295919A1 (en) 2010-08-31 2013-03-07 Genentech, Inc. Biomarkers and methods of treatment
CN103328511B (zh) 2010-09-10 2016-01-20 埃派斯进有限公司 抗-IL-1β抗体及其使用方法
IL319612A (en) 2010-09-29 2025-05-01 Seagen Inc Antibody drug conjugates (ADC) that bind to 191P4D12 proteins
EP3828205A1 (en) 2010-10-01 2021-06-02 Oxford BioTherapeutics Ltd Anti-ror1 antibodies
DK2625197T3 (en) 2010-10-05 2016-10-03 Genentech Inc Smoothened MUTANT AND METHODS OF USING THE SAME
US8772457B2 (en) 2010-11-10 2014-07-08 Genentech, Inc. BACE1 antibodies
WO2012083132A2 (en) 2010-12-16 2012-06-21 Genentech, Inc. Diagnosis and treatments relating to th2 inhibition
NZ610976A (en) 2010-12-20 2015-07-31 Genentech Inc Anti-mesothelin antibodies and immunoconjugates
SG191219A1 (en) 2010-12-22 2013-07-31 Genentech Inc Anti-pcsk9 antibodies and methods of use
EP2655413B1 (en) 2010-12-23 2019-01-16 F.Hoffmann-La Roche Ag Polypeptide-polynucleotide-complex and its use in targeted effector moiety delivery
JOP20210044A1 (ar) 2010-12-30 2017-06-16 Takeda Pharmaceuticals Co الأجسام المضادة لـ cd38
WO2012092539A2 (en) 2010-12-31 2012-07-05 Takeda Pharmaceutical Company Limited Antibodies to dll4 and uses thereof
CN103649117B (zh) 2011-02-04 2016-09-14 霍夫曼-拉罗奇有限公司 Fc变体及其生成方法
US10689447B2 (en) 2011-02-04 2020-06-23 Genentech, Inc. Fc variants and methods for their production
CA2827170A1 (en) 2011-02-11 2012-08-16 David M. Hilbert Monovalent and multivalent multispecific complexes and uses thereof
US8916160B2 (en) 2011-02-14 2014-12-23 Theraclone Sciences, Inc. Compositions and methods for the therapy and diagnosis of influenza
RU2013144392A (ru) 2011-03-03 2015-04-10 Апексиджен, Инк. Антитела к рецептору il-6 и способы применения
EP2683740B1 (en) 2011-03-10 2018-07-04 Omeros Corporation Generation of anti-fn14 monoclonal antibodies by ex-vivo accelerated antibody evolution
KR20140012131A (ko) 2011-03-15 2014-01-29 테라클론 사이언시스, 아이엔씨. 인플루엔자의 치료 및 진단을 위한 조성물 및 방법
HUE041335T2 (hu) 2011-03-29 2019-05-28 Roche Glycart Ag Antitest FC-variánsok
MX342240B (es) 2011-04-07 2016-09-21 Genentech Inc Anticuerpos anti-fgfr4 y metodos de uso.
AU2012244816B2 (en) 2011-04-20 2015-12-10 Roche Glycart Ag Method and constructs for the pH dependent passage of the blood-brain-barrier
CN106928362B (zh) 2011-04-29 2021-10-26 埃派斯进有限公司 抗-cd40抗体及其使用方法
LT2710035T (lt) 2011-05-16 2017-06-26 F. Hoffmann-La Roche Ag Fgfr1 agonistai ir jų naudojimo būdai
DK2714738T3 (en) 2011-05-24 2019-01-28 Zyngenia Inc MULTIVALENT AND MONOVALENT MULTISPECIFIC COMPLEXES AND THEIR APPLICATIONS
US20140105915A1 (en) 2011-05-27 2014-04-17 Glaxo Group Limited Bcma (cd269/tnfrsf17) - binding proteins
US20130004484A1 (en) 2011-06-30 2013-01-03 Genentech, Inc. Anti-c-met antibody formulations
WO2013022855A1 (en) 2011-08-05 2013-02-14 Xencor, Inc. Antibodies with modified isoelectric points and immunofiltering
US9102724B2 (en) 2011-08-12 2015-08-11 Omeros Corporation Anti-FZD10 monoclonal antibodies and methods for their use
RU2014109985A (ru) 2011-08-17 2015-09-27 Дженентек, Инк. Ингибирование ангиогенеза в рефрактерных опухолях
US20140363438A1 (en) 2011-08-17 2014-12-11 Genentech, Inc. Neuregulin antibodies and uses thereof
MX356947B (es) 2011-08-23 2018-06-20 Roche Glycart Ag Anticuerpos bioespecíficos específicos para antígenos que activan células t y un antígeno tumoral y métodos de uso.
CN103781801B (zh) 2011-08-23 2018-02-09 罗切格利卡特公司 包含两个Fab片段的无Fc的抗体及使用方法
WO2013033069A1 (en) 2011-08-30 2013-03-07 Theraclone Sciences, Inc. Human rhinovirus (hrv) antibodies
MX2014003094A (es) 2011-09-15 2014-04-25 Genentech Inc Metodos para promover diferenciacion.
KR20140064971A (ko) 2011-09-19 2014-05-28 제넨테크, 인크. c-met 길항제 및 B-raf 길항제를 포함하는 조합 치료
HK1200850A1 (en) 2011-09-23 2015-08-14 罗氏格黎卡特股份公司 Bispecific anti-egfr/anti igf-1r antibodies
US9663573B2 (en) 2011-10-05 2017-05-30 Genentech, Inc. Methods of treating liver conditions using Notch2 antagonists
US12466897B2 (en) 2011-10-10 2025-11-11 Xencor, Inc. Heterodimeric human IgG1 polypeptides with isoelectric point modifications
CA3182462A1 (en) 2011-10-10 2013-04-18 Xencor, Inc. A method for purifying antibodies
US10851178B2 (en) 2011-10-10 2020-12-01 Xencor, Inc. Heterodimeric human IgG1 polypeptides with isoelectric point modifications
MX355128B (es) 2011-10-14 2018-04-06 Genentech Inc Péptidos inhibidores de bace1 y uso de los mismos para el tratamiento de enfermedades o trastornos neurológicos.
LT2766393T (lt) 2011-10-14 2018-10-10 F. Hoffmann-La Roche Ag Antikūnai prieš htra1 ir jų naudojimo būdai
EP2766000A2 (en) 2011-10-15 2014-08-20 F.Hoffmann-La Roche Ag Scd1 antagonists for treating cancer
EP2776051A4 (en) 2011-10-28 2015-06-17 Hoffmann La Roche THERAPEUTIC COMBINATIONS AND METHOD FOR THE TREATMENT OF MELANOMA
PL3257564T5 (pl) 2011-11-02 2024-10-07 F. Hoffmann-La Roche Ag Chromatografia elucyjna z przeładowaniem
CA2854153A1 (en) 2011-11-02 2013-05-10 Apexigen, Inc. Anti-kdr antibodies and methods of use
US20140315817A1 (en) 2011-11-18 2014-10-23 Eleven Biotherapeutics, Inc. Variant serum albumin with improved half-life and other properties
BR112014012005A2 (pt) 2011-11-21 2017-12-19 Genentech Inc composições, métodos, formulação farmacêutica e artigo
US10117932B2 (en) 2011-12-08 2018-11-06 Biotest Ag Uses of immunoconjugates targeting CD138
RU2658603C2 (ru) 2011-12-15 2018-06-21 Ф.Хоффманн-Ля Рош Аг Антитела против человеческого csf-1r и их применения
US20130195851A1 (en) 2011-12-23 2013-08-01 Genentech, Inc. Articles of manufacture and methods for co-administration of antibodies
US20150011431A1 (en) 2012-01-09 2015-01-08 The Scripps Research Institute Humanized antibodies
US10774132B2 (en) 2012-01-09 2020-09-15 The Scripps Research Instittue Ultralong complementarity determining regions and uses thereof
IN2014DN05885A (enExample) 2012-01-18 2015-06-05 Hoffmann La Roche
CA2862424A1 (en) 2012-01-18 2013-07-25 Genentech, Inc. Methods of using fgf19 modulators
JP6486686B2 (ja) 2012-02-10 2019-03-20 ジェネンテック， インコーポレイテッド 単鎖抗体及び他のヘテロ多量体
WO2013120056A1 (en) 2012-02-11 2013-08-15 Genentech, Inc. R-spondin translocations and methods using the same
BR112014018005B1 (pt) 2012-02-15 2021-06-29 F. Hoffmann-La Roche Ag Uso de um complexo não covalente imobilizado
MX2014010278A (es) 2012-03-16 2015-03-05 Novozymes Biopharma Dk As Variantes de albumina.
AR090549A1 (es) 2012-03-30 2014-11-19 Genentech Inc Anticuerpos anti-lgr5 e inmunoconjugados
US10130714B2 (en) 2012-04-14 2018-11-20 Academia Sinica Enhanced anti-influenza agents conjugated with anti-inflammatory activity
US9056910B2 (en) 2012-05-01 2015-06-16 Genentech, Inc. Anti-PMEL17 antibodies and immunoconjugates
WO2013170191A1 (en) 2012-05-11 2013-11-14 Genentech, Inc. Methods of using antagonists of nad biosynthesis from nicotinamide
EP2861624A1 (en) 2012-06-15 2015-04-22 F. Hoffmann-La Roche AG Anti-pcsk9 antibodies, formulations, dosing, and methods of use
CN104395339A (zh) 2012-06-27 2015-03-04 弗·哈夫曼-拉罗切有限公司 用于选择并产生含有至少两种不同结合实体的定制高度选择性和多特异性靶向实体的方法及其用途
MX2014014804A (es) 2012-06-27 2015-02-12 Hoffmann La Roche Metodo para la elaboracion de conjugados de la region fc de anticuerpos que comprenden por lo menos una entidad de union que se une especificamente a un objetivo y usos del mismo.
WO2014001326A1 (en) 2012-06-27 2014-01-03 F. Hoffmann-La Roche Ag Method for the selection and production of tailor-made, selective and multi-specific therapeutic molecules comprising at least two different targeting entities and uses thereof
KR20150030755A (ko) 2012-07-04 2015-03-20 에프. 호프만-라 로슈 아게 항-바이오틴 항체 및 사용 방법
AU2013285422B2 (en) 2012-07-04 2017-04-27 F. Hoffmann-La Roche Ag Covalently linked antigen-antibody conjugates
CN104394886B (zh) 2012-07-04 2017-05-24 弗·哈夫曼-拉罗切有限公司 抗茶碱抗体及使用方法
MX361337B (es) 2012-07-13 2018-12-04 Roche Glycart Ag Anticuerpos biespecificos anti-factor de crecimiento endotelial vascular humano (vegf) / anti-angiopoyetina-2 humana (ang-2) y su uso en el tratamiento de enfermedades vasculares oculares.
JP6302909B2 (ja) 2012-08-18 2018-03-28 アカデミア シニカＡｃａｄｅｍｉａ Ｓｉｎｉｃａ シアリダーゼの同定および画像化のための細胞透過性プローブ
KR102355959B1 (ko) 2012-08-23 2022-01-27 어젠시스 인코포레이티드 158p1d7 단백질에 결합하는 항체 약물 컨쥬게이트(ａｄｃ)
IN2015DN01967A (enExample) 2012-09-19 2015-08-14 Abbvie Biotherapeutics Inc
US10087250B2 (en) 2012-10-08 2018-10-02 Roche Glycart Ag Fc-free antibodies comprising two fab-fragments and methods of use
KR102270618B1 (ko) 2012-10-30 2021-06-30 아펙시젠, 인코포레이티드 항-cd40 항체 및 사용 방법
CA2889764C (en) 2012-11-01 2023-10-10 Martin Lipp An antibody that binds cd269 (bcma) suitable for use in the treatment of plasma cell diseases such as multiple myeloma and autoimmune diseases
MX2015005757A (es) 2012-11-08 2015-11-18 Hoffmann La Roche Proteinas ligantes de antigeno her3 de union a la horquilla beta de her3.
CN105452290A (zh) 2012-11-08 2016-03-30 诺维信生物制药丹麦公司 白蛋白变体
MA38176A1 (fr) 2012-11-13 2017-06-30 Genentech Inc Nouvel anticorps anti-hemagglutinine, utile pour le traitement, l'inhibition ou la prévention de l’infection virale a grippe a
BR112015011011A2 (pt) 2012-11-15 2019-12-17 Genentech Inc cromatografia por troca de íon com gradiente de ph mediada por força iônica
WO2014080251A1 (en) 2012-11-24 2014-05-30 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules
US20140154255A1 (en) 2012-11-30 2014-06-05 Abbvie Biotherapeutics Inc. Anti-vegf antibodies and their uses
WO2014107739A1 (en) 2013-01-07 2014-07-10 Eleven Biotherapeutics, Inc. Antibodies against pcsk9
CA2898100C (en) 2013-01-14 2023-10-10 Xencor, Inc. Novel heterodimeric proteins
US10968276B2 (en) 2013-03-12 2021-04-06 Xencor, Inc. Optimized anti-CD3 variable regions
US10131710B2 (en) 2013-01-14 2018-11-20 Xencor, Inc. Optimized antibody variable regions
US10487155B2 (en) 2013-01-14 2019-11-26 Xencor, Inc. Heterodimeric proteins
US11053316B2 (en) 2013-01-14 2021-07-06 Xencor, Inc. Optimized antibody variable regions
US9701759B2 (en) 2013-01-14 2017-07-11 Xencor, Inc. Heterodimeric proteins
US9605084B2 (en) 2013-03-15 2017-03-28 Xencor, Inc. Heterodimeric proteins
WO2014113510A1 (en) 2013-01-15 2014-07-24 Xencor, Inc. Rapid clearance of antigen complexes using novel antibodies
HK1211235A1 (en) 2013-02-22 2016-05-20 霍夫曼-拉罗奇有限公司 Methods of treating cancer and preventing drug resistance
US20140242083A1 (en) 2013-02-26 2014-08-28 Roche Glycart Ag Anti-mcsp antibodies
KR20150123250A (ko) 2013-03-06 2015-11-03 제넨테크, 인크. 암 약물 내성의 치료 및 예방 방법
WO2014159835A1 (en) 2013-03-14 2014-10-02 Genentech, Inc. Anti-b7-h4 antibodies and immunoconjugates
US9562099B2 (en) 2013-03-14 2017-02-07 Genentech, Inc. Anti-B7-H4 antibodies and immunoconjugates
RU2015139054A (ru) 2013-03-14 2017-04-19 Дженентек, Инк. Способы лечения рака и профилактики лекарственной резистентности рака
EP3421495A3 (en) 2013-03-15 2019-05-15 Xencor, Inc. Modulation of t cells with bispecific antibodies and fc fusions
AR095517A1 (es) 2013-03-15 2015-10-21 Genentech Inc ANTICUERPOS CONTRA EL RECEPTOR QUIMIOATRAYENTE EXPRESADO EN CÉLULAS T HELPER 2 (ANTI-CRTh2) Y MÉTODOS DE USO
US10106624B2 (en) 2013-03-15 2018-10-23 Xencor, Inc. Heterodimeric proteins
CA2907181C (en) 2013-03-15 2023-10-17 Viktor Roschke Multivalent and monovalent multispecific complexes and their uses
US10858417B2 (en) 2013-03-15 2020-12-08 Xencor, Inc. Heterodimeric proteins
EP2968537A1 (en) 2013-03-15 2016-01-20 Genentech, Inc. Methods of treating cancer and preventing cancer drug resistance
HK1211963A1 (en) 2013-03-15 2016-06-03 豪夫迈．罗氏有限公司 Compositions and methods for diagnosis and treatment of hepatic cancers
AR095199A1 (es) 2013-03-15 2015-09-30 Genzyme Corp Anticuerpos anti-cd52
MX2015012551A (es) 2013-03-15 2016-10-26 Abbvie Biotechnology Ltd Anticuerpos anti-cd25 y sus usos.
RU2015144033A (ru) 2013-03-15 2017-04-26 Эббви Байотекнолоджи Лтд. Антитела против cd25 и их применения
RU2661111C2 (ru) 2013-03-15 2018-07-11 Ац Иммуне С.А. Антитела к тау и способы применения
JP6594855B2 (ja) 2013-03-15 2019-10-23 ゼンコア インコーポレイテッド ヘテロ二量体タンパク質
US10519242B2 (en) 2013-03-15 2019-12-31 Xencor, Inc. Targeting regulatory T cells with heterodimeric proteins
US20140377253A1 (en) 2013-03-15 2014-12-25 Abbvie Biotherapeutics Inc. Fc variants
KR20220053691A (ko) 2013-03-15 2022-04-29 제넨테크, 인크. Pd-1 및 pd-l1 관련 상태를 치료하기 위한 바이오마커 및 방법
AR095882A1 (es) 2013-04-22 2015-11-18 Hoffmann La Roche Terapia de combinación de anticuerpos contra csf-1r humano con un agonista de tlr9
US20160068613A1 (en) 2013-04-29 2016-03-10 Hoffmann-La Roche Inc. Fc-receptor binding modified asymmetric antibodies and methods of use
WO2014179657A1 (en) 2013-05-03 2014-11-06 Eleven Biotherapeutics, Inc. Albumin variants binding to fcrn
PH12021550015A1 (en) 2013-05-20 2022-05-11 Genentech Inc Anti-transferrin receptor antibodies and methods of use
EP3013365B1 (en) 2013-06-26 2019-06-05 Academia Sinica Rm2 antigens and use thereof
WO2014210564A1 (en) 2013-06-27 2014-12-31 Academia Sinica Glycan conjugates and use thereof
RU2016104542A (ru) 2013-07-12 2017-08-17 Дженентек, Инк. Осуществление оптимизации входных условий ионообменной хроматографии
US20160168231A1 (en) 2013-07-18 2016-06-16 Fabrus, Inc. Antibodies with ultralong complementarity determining regions
CN111518199A (zh) 2013-07-18 2020-08-11 图鲁斯生物科学有限责任公司 具有超长互补决定区的人源化抗体
CN105722534B (zh) 2013-08-01 2019-05-31 艾更斯司股份有限公司 结合cd37蛋白的抗体药物偶联物(adc)
WO2015035044A2 (en) 2013-09-04 2015-03-12 Abbvie Biotherapeutics Inc. Fc VARIANTS WITH IMPROVED ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY
WO2015035180A1 (en) 2013-09-05 2015-03-12 Genentech, Inc. Method for chromatography reuse
CN105682666B (zh) 2013-09-06 2021-06-01 中央研究院 使用醣脂激活人类iNKT细胞
AR097584A1 (es) 2013-09-12 2016-03-23 Hoffmann La Roche Terapia de combinación de anticuerpos contra el csf-1r humano y anticuerpos contra el pd-l1 humano
AR097685A1 (es) 2013-09-17 2016-04-06 Genentech Inc Métodos de uso de anticuerpos anti-lgr5
CN105745224B (zh) 2013-10-11 2019-11-05 牛津生物疗法有限公司 用于治疗癌症的针对ly75的偶联抗体
BR112016008477A2 (pt) 2013-10-18 2017-10-03 Genentech Inc Corpos, ácido nucleico, célula hospedeira, método de produção de um anticorpo, imunoconjugado, formulação farmacêutica e usos do anticorpo
PE20161413A1 (es) 2013-11-04 2017-01-10 Stemcentrx Inc Conjugados de anticuerpo anti-efna4-farmaco
AU2014362238A1 (en) 2013-12-13 2016-06-09 Genentech, Inc. Anti-CD33 antibodies and immunoconjugates
EA201691023A1 (ru) 2013-12-16 2016-10-31 Дженентек, Инк. Пептидомиметические соединения и их конъюгаты антитела с лекарственным средством
TWI670283B (zh) 2013-12-23 2019-09-01 美商建南德克公司 抗體及使用方法
CN105873616B (zh) 2014-01-03 2020-06-05 豪夫迈·罗氏有限公司 共价连接的多肽毒素-抗体缀合物
KR102278979B1 (ko) 2014-01-03 2021-07-19 에프. 호프만-라 로슈 아게 공유적으로 연결된 헬리카-항-헬리카 항체 접합체 및 그의 용도
ES2895752T3 (es) 2014-01-03 2022-02-22 Hoffmann La Roche Anticuerpos biespecíficos anti-hapteno/anti-receptor de la barrera hematoencefálica, complejos de los mismos y su uso como lanzaderas a través de la barrera hematoencefálica
US10150818B2 (en) 2014-01-16 2018-12-11 Academia Sinica Compositions and methods for treatment and detection of cancers
JP2017507118A (ja) 2014-01-16 2017-03-16 アカデミア シニカＡｃａｄｅｍｉａ Ｓｉｎｉｃａ がんの処置および検出のための組成物および方法
EP3096797A1 (en) 2014-01-24 2016-11-30 F. Hoffmann-La Roche AG Methods of using anti-steap1 antibodies and immunoconjugates
WO2015120075A2 (en) 2014-02-04 2015-08-13 Genentech, Inc. Mutant smoothened and methods of using the same
US9518121B2 (en) 2014-02-12 2016-12-13 Genentech, Inc. Anti-Jagged1 antibodies and methods of use
WO2015127405A2 (en) 2014-02-21 2015-08-27 Genentech, Inc. Anti-il-13/il-17 bispecific antibodies and uses thereof
PT3122757T (pt) 2014-02-28 2023-11-03 Hangzhou Dac Biotech Co Ltd Ligantes carregados e as suas utilizações em conjugação
MX2016011637A (es) 2014-03-14 2017-04-13 Genentech Inc Metodos y composiciones para secrecion de polipeptidos heterologos.
CA2942101A1 (en) 2014-03-21 2015-09-24 Abbvie Inc. Anti-egfr antibodies and antibody drug conjugates
RU2688349C2 (ru) 2014-03-21 2019-05-21 Ф. Хоффманн-Ля Рош Аг In vitro прогнозирование времени полужизни антител in vivo
EP3122900A1 (en) 2014-03-24 2017-02-01 F. Hoffmann-La Roche AG Cancer treatment with c-met antagonists and correlation of the latter with hgf expression
CN106415244B (zh) 2014-03-27 2020-04-24 中央研究院 反应性标记化合物及其用途
MX385936B (es) 2014-03-28 2025-03-11 Xencor Inc Anticuerpos biespecíficos que se unen a cd38 y cd3.
MX2016012779A (es) 2014-03-31 2017-04-27 Genentech Inc Terapia de combinacion con agentes antiangiogénesis y agonistas de unión a ox40.
AU2015241037B2 (en) 2014-03-31 2020-10-15 Genentech, Inc. Anti-OX40 antibodies and methods of use
HK1232127A1 (zh) 2014-04-11 2018-01-05 Medimmune, Llc 双特异性her2抗体
KR20230164192A (ko) 2014-05-06 2023-12-01 제넨테크, 인크. 포유동물 세포를 사용한 이종다량체 단백질의 생산
BR112016027222A2 (pt) 2014-05-22 2018-01-30 Genentech Inc anticorpos isolados, ácido nucleico isolado, célula hospedeira, método de produção de um anticorpo, imunoconjugado, formulação farmacêutica, métodos de tratamento de um indivíduo com um câncer, de inibição da proliferação de uma célula, de detecção de gpc3 humano e de detecção de um câncer
KR20170005016A (ko) 2014-05-23 2017-01-11 제넨테크, 인크. MiT 바이오마커 및 그의 사용 방법
US20150344585A1 (en) 2014-05-27 2015-12-03 Academia Sinica Anti-cd20 glycoantibodies and uses thereof
TWI679020B (zh) 2014-05-27 2019-12-11 中央研究院 抗ｈｅｒ２醣抗體及其用途
TWI717319B (zh) 2014-05-27 2021-02-01 中央研究院 得自類桿菌屬之岩藻糖苷酶及其用途
US10118969B2 (en) 2014-05-27 2018-11-06 Academia Sinica Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
TWI732738B (zh) 2014-05-28 2021-07-11 中央研究院 抗TNF-α醣抗體及其用途
JP2017517552A (ja) 2014-06-13 2017-06-29 ジェネンテック， インコーポレイテッド 抗癌剤耐性の治療及び防止方法
KR20170026362A (ko) 2014-06-26 2017-03-08 에프. 호프만-라 로슈 아게 항-ｂｒｄｕ 항체 및 사용 방법
CN106488775A (zh) 2014-07-11 2017-03-08 基因泰克公司 Notch途径抑制
EP3194449A1 (en) 2014-07-24 2017-07-26 Xencor, Inc. Rapid clearance of antigen complexes using novel antibodies
TWI751102B (zh) 2014-08-28 2022-01-01 美商奇諾治療有限公司 對ｃｄ１９具專一性之抗體及嵌合抗原受體
ES3034398T3 (en) 2014-08-28 2025-08-18 Bioatla Inc Conditionally active chimeric antigen receptors for modified t-cells
TWI745275B (zh) 2014-09-08 2021-11-11 中央研究院 使用醣脂激活人類ｉＮＫＴ細胞
MX2017003123A (es) 2014-09-12 2017-05-12 Genentech Inc Anticuerpos y conjugados modificados geneticamente con cisteina.
WO2016040724A1 (en) 2014-09-12 2016-03-17 Genentech, Inc. Anti-b7-h4 antibodies and immunoconjugates
CR20170095A (es) 2014-09-12 2017-07-19 Genentech Inc Anticuerpos anti-cll-1 e inmunoconjugados referencias recíprocas con solicitudes relacionadas
PE20170935A1 (es) 2014-09-12 2017-07-13 Genentech Inc Anticuerpos anti-her2 e inmunoconjugados
EP3262071B8 (en) 2014-09-23 2022-05-18 F. Hoffmann-La Roche AG Method of using anti-cd79b immunoconjugates
CA2962783A1 (en) 2014-10-01 2016-04-07 Medimmune, Llc Method of conjugating a polypeptide
CN107074938A (zh) 2014-10-16 2017-08-18 豪夫迈·罗氏有限公司 抗‑α‑突触核蛋白抗体和使用方法
WO2016070062A2 (en) 2014-10-31 2016-05-06 Genentech, Inc. Anti-il-17a and il-17f cross reactive antibody variants and compositions comprising and methods of making and using same
RU2017119231A (ru) 2014-11-03 2018-12-06 Дженентек, Инк. Способы и биомаркеры для прогнозирования эффективности и оценки лечения агонистом ох40
SG11201703448QA (en) 2014-11-03 2017-05-30 Genentech Inc Assays for detecting t cell immune subsets and methods of use thereof
CA2961439A1 (en) 2014-11-05 2016-05-12 Genentech, Inc. Anti-fgfr2/3 antibodies and methods using same
WO2016073157A1 (en) 2014-11-06 2016-05-12 Genentech, Inc. Anti-ang2 antibodies and methods of use thereof
PT3215528T (pt) 2014-11-06 2019-10-11 Hoffmann La Roche Variantes da região fc com ligação modificada ao fcrn e métodos de utilização
CA2960297A1 (en) 2014-11-10 2016-05-19 Genentech, Inc. Anti-interleukin-33 antibodies and uses thereof
JP6859259B2 (ja) 2014-11-19 2021-04-14 ジェネンテック， インコーポレイテッド ＢＡＣＥｌに対する抗体及び神経疾患免疫療法のためのその使用
CN107001473B (zh) 2014-11-19 2021-07-09 豪夫迈·罗氏有限公司 抗-运铁蛋白受体抗体及使用方法
JP6993228B2 (ja) 2014-11-19 2022-03-03 ジェネンテック， インコーポレイテッド 抗トランスフェリン受容体／抗ｂａｃｅ１多重特異性抗体および使用方法
US10259887B2 (en) 2014-11-26 2019-04-16 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
MX2017006918A (es) 2014-11-26 2018-01-25 Xencor Inc Anticuerpos heterodimericos que se unen a cd3 y cd38.
HRP20211273T1 (hr) 2014-11-26 2021-11-12 Xencor, Inc. Heterodimerna protutijela koja vežu cd3 i cd20
PL3227332T3 (pl) 2014-12-03 2020-06-15 F. Hoffmann-La Roche Ag Wielospecyficzne przeciwciała
SG11201704449VA (en) 2014-12-05 2017-06-29 Genentech Inc ANTI-CD79b ANTIBODIES AND METHODS OF USE
CA2966365A1 (en) 2014-12-10 2016-06-16 Genentech, Inc. Blood brain barrier receptor antibodies and methods of use
TWI617580B (zh) 2014-12-19 2018-03-11 中外製藥股份有限公司 抗ｃ５抗體及使用方法
MY181199A (en) 2014-12-19 2020-12-21 Chugai Pharmaceutical Co Ltd Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use
EP3237449A2 (en) 2014-12-22 2017-11-01 Xencor, Inc. Trispecific antibodies
US10495645B2 (en) 2015-01-16 2019-12-03 Academia Sinica Cancer markers and methods of use thereof
AR103442A1 (es) 2015-01-16 2017-05-10 Juno Therapeutics Inc Anticuerpos y receptores de antígenos quiméricos específicos de ror1
US9975965B2 (en) 2015-01-16 2018-05-22 Academia Sinica Compositions and methods for treatment and detection of cancers
WO2016117346A1 (en) 2015-01-22 2016-07-28 Chugai Seiyaku Kabushiki Kaisha A combination of two or more anti-c5 antibodies and methods of use
CN112430268A (zh) 2015-01-24 2021-03-02 中央研究院 癌症标记及其使用方法
CA2972072A1 (en) 2015-01-24 2016-07-28 Academia Sinica Novel glycan conjugates and methods of use thereof
EP3253784B1 (en) 2015-02-04 2020-05-06 Genentech, Inc. Mutant smoothened and methods of using the same
CN107108729A (zh) 2015-02-05 2017-08-29 中外制药株式会社 包含离子浓度依赖性的抗原结合结构域的抗体，fc区变体，il‑8‑结合抗体，及其应用
WO2016141387A1 (en) 2015-03-05 2016-09-09 Xencor, Inc. Modulation of t cells with bispecific antibodies and fc fusions
EP3286227A2 (en) 2015-04-24 2018-02-28 F. Hoffmann-La Roche AG Multispecific antigen-binding proteins
CN115932273A (zh) 2015-04-24 2023-04-07 豪夫迈·罗氏有限公司 鉴定包含结合多肽的细菌的方法
EP3778640A1 (en) 2015-05-01 2021-02-17 Genentech, Inc. Masked anti-cd3 antibodies and methods of use
EP4450524A3 (en) 2015-05-11 2025-05-14 F. Hoffmann-La Roche AG Compositions and methods of treating lupus nephritis
MX2017014381A (es) 2015-05-12 2018-03-02 Genentech Inc Metodos terapeuticos y diagnosticos para cancer.
SI3303400T1 (sl) 2015-05-28 2021-01-29 Genentech, Inc. Na celicah osnovan test za detektiranje anti-CD3 homodimerov
CN107771182A (zh) 2015-05-29 2018-03-06 豪夫迈·罗氏有限公司 人源化抗埃博拉病毒糖蛋白抗体和使用方法
JP7144935B2 (ja) 2015-05-29 2022-09-30 ジェネンテック， インコーポレイテッド 癌のための治療方法及び診断方法
EP3303399A1 (en) 2015-06-08 2018-04-11 H. Hoffnabb-La Roche Ag Methods of treating cancer using anti-ox40 antibodies
KR20180025888A (ko) 2015-06-08 2018-03-09 제넨테크, 인크. 항-ox40 항체 및 pd-1 축 결합 길항제를 사용하여 암을 치료하는 방법
WO2016204966A1 (en) 2015-06-16 2016-12-22 Genentech, Inc. Anti-cd3 antibodies and methods of use
CN107847568B (zh) 2015-06-16 2022-12-20 豪夫迈·罗氏有限公司 抗cll-1抗体和使用方法
EP3310814B1 (en) 2015-06-16 2023-08-02 F. Hoffmann-La Roche AG Humanized and affinity matured antibodies to fcrh5 and methods of use
KR20180012859A (ko) 2015-06-17 2018-02-06 제넨테크, 인크. 항-her2 항체 및 이용 방법
IL302486A (en) 2015-06-24 2023-06-01 Hoffmann La Roche Antibodies against the transnephrine receptor with adapted affinity
CN107531788B (zh) 2015-06-24 2022-06-21 豪夫迈·罗氏有限公司 对her2和血脑屏障受体特异性的三特异性抗体及使用方法
EP3313885A1 (en) 2015-06-29 2018-05-02 H. Hoffnabb-La Roche Ag Type ii anti-cd20 antibody for use in organ transplantation
CN108449940B (zh) 2015-07-12 2021-06-08 杭州多禧生物科技有限公司 与细胞结合分子的共轭偶联的桥连接体
US9839687B2 (en) 2015-07-15 2017-12-12 Suzhou M-Conj Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
US10669343B2 (en) 2015-08-05 2020-06-02 Janssen Biotech, Inc. Anti-CD154 antibodies and methods of using them
CN105384825B (zh) 2015-08-11 2018-06-01 南京传奇生物科技有限公司 一种基于单域抗体的双特异性嵌合抗原受体及其应用
CA2989966C (en) 2015-08-20 2024-04-30 Albumedix A/S Albumin variants and conjugates
CA2996205A1 (en) 2015-09-20 2017-03-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Monoclonal antibodies specific for fibroblast growth factor receptor 4 (fgfr4) and methods of their use
CN116987187A (zh) 2015-09-23 2023-11-03 豪夫迈·罗氏有限公司 抗-vegf抗体的优化的变体
CA2999917A1 (en) 2015-09-24 2017-03-30 Abvitro Llc Hiv antibody compositions and methods of use
MY186016A (en) 2015-09-25 2021-06-14 Genentech Inc Anti-tigit antibodies and methods of use
CN108368510B (zh) 2015-09-30 2023-09-01 詹森生物科技公司 特异性结合人cd40的激动性抗体和使用方法
RU2746409C1 (ru) 2015-10-02 2021-04-13 Ф. Хоффманн-Ля Рош Аг Антитела к pd1 и способы их применения
CN114057885A (zh) 2015-10-02 2022-02-18 豪夫迈·罗氏有限公司 双特异性抗人cd20/人转铁蛋白受体抗体及使用方法
CN114773481B (zh) 2015-10-02 2025-04-29 豪夫迈·罗氏有限公司 对pd1和tim3特异性的双特异性抗体
AR106189A1 (es) 2015-10-02 2017-12-20 Hoffmann La Roche ANTICUERPOS BIESPECÍFICOS CONTRA EL A-b HUMANO Y EL RECEPTOR DE TRANSFERRINA HUMANO Y MÉTODOS DE USO
MA43354A (fr) 2015-10-16 2018-08-22 Genentech Inc Conjugués médicamenteux à pont disulfure encombré
WO2017066714A1 (en) 2015-10-16 2017-04-20 Compugen Ltd. Anti-vsig1 antibodies and drug conjugates
MA45326A (fr) 2015-10-20 2018-08-29 Genentech Inc Conjugués calichéamicine-anticorps-médicament et procédés d'utilisation
EP3184547A1 (en) 2015-10-29 2017-06-28 F. Hoffmann-La Roche AG Anti-tpbg antibodies and methods of use
JP6920292B2 (ja) 2015-10-30 2021-08-18 ジェネンテック， インコーポレイテッド ヒンジが修飾された抗体断片及び作製方法
MY198562A (en) 2015-11-03 2023-09-05 Janssen Biotech Inc Antibodies specifically binding pd-1 and their uses
EP3371217B1 (en) 2015-11-08 2025-06-11 F. Hoffmann-La Roche AG Methods of screening for multispecific antibodies
JP7058219B2 (ja) 2015-12-07 2022-04-21 ゼンコア インコーポレイテッド Ｃｄ３及びｐｓｍａに結合するヘテロ二量体抗体
KR102850929B1 (ko) 2015-12-09 2025-08-27 에프. 호프만-라 로슈 아게 항-약물 항체의 형성을 감소시키기 위한 ii형 항-cd20 항체
EP3178848A1 (en) 2015-12-09 2017-06-14 F. Hoffmann-La Roche AG Type ii anti-cd20 antibody for reducing formation of anti-drug antibodies
IL259256B2 (en) 2015-12-18 2023-02-01 Chugai Pharmaceutical Co Ltd Anti-c5 antibodies and methods of use
WO2017104783A1 (en) 2015-12-18 2017-06-22 Chugai Seiyaku Kabushiki Kaisha Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use
WO2017132279A1 (en) 2016-01-25 2017-08-03 Genentech, Inc. Methods for assaying t-cell dependent bispecific antibodies
BR112018015259A2 (pt) 2016-01-27 2018-12-18 Medimmune Llc métodos para preparação de anticorpos com um padrão de glicosilação definido
EP3411396A1 (en) 2016-02-04 2018-12-12 Curis, Inc. Mutant smoothened and methods of using the same
KR102500659B1 (ko) 2016-02-29 2023-02-16 제넨테크, 인크. 암에 대한 치료 및 진단 방법
TW201808978A (zh) 2016-03-08 2018-03-16 中央研究院 N-聚醣及其陣列之模組化合成方法
CA3056374A1 (en) 2016-04-13 2017-10-19 Orimabs Ltd. Anti-psma antibodies and use thereof
WO2017180864A1 (en) 2016-04-14 2017-10-19 Genentech, Inc. Anti-rspo3 antibodies and methods of use
CA3020864A1 (en) 2016-04-15 2017-10-19 Macrogenics, Inc. Novel b7-h3-binding molecules, antibody drug conjugates thereof and methods of use thereof
JP2019515670A (ja) 2016-04-15 2019-06-13 ジェネンテック， インコーポレイテッド がんをモニタリングし治療するための方法
SG11201808994YA (en) 2016-04-15 2018-11-29 Bioatla Llc Anti-axl antibodies, antibody fragments and their immunoconjugates and uses thereof
KR20190003958A (ko) 2016-04-15 2019-01-10 제넨테크, 인크. 암의 치료 및 모니터링 방법
SG11201809620UA (en) 2016-05-02 2018-11-29 Hoffmann La Roche The contorsbody - a single chain target binder
WO2017196847A1 (en) 2016-05-10 2017-11-16 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Variable new antigen receptor (vnar) antibodies and antibody conjugates targeting tumor and viral antigens
JP7089483B2 (ja) 2016-05-11 2022-06-22 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト 修飾された抗テネイシン抗体及び使用方法
ES2930255T3 (es) 2016-05-13 2022-12-09 Bioatla Inc Anticuerpos anti-Ror2, fragmentos de anticuerpos, sus inmunoconjugados y usos de los mismos
US20170370906A1 (en) 2016-05-27 2017-12-28 Genentech, Inc. Bioanalytical analysis of site-specific antibody drug conjugates
EP3252078A1 (en) 2016-06-02 2017-12-06 F. Hoffmann-La Roche AG Type ii anti-cd20 antibody and anti-cd20/cd3 bispecific antibody for treatment of cancer
CN110603266A (zh) 2016-06-02 2019-12-20 豪夫迈·罗氏有限公司 用于治疗癌症的ii型抗cd20抗体和抗cd20/cd3双特异性抗体
WO2017214182A1 (en) 2016-06-07 2017-12-14 The United States Of America. As Represented By The Secretary, Department Of Health & Human Services Fully human antibody targeting pdi for cancer immunotherapy
JP2019522643A (ja) 2016-06-08 2019-08-15 アッヴィ・インコーポレイテッド 抗ｃｄ９８抗体及び抗体薬物コンジュゲート
EP3468598A1 (en) 2016-06-08 2019-04-17 AbbVie Inc. Anti-cd98 antibodies and antibody drug conjugates
PT3468997T (pt) 2016-06-08 2023-12-07 Debra Zack Tratamento de doenças relacionadas com igg4 com anticorpos anti-cd19 com ligação cruzada a cd32b
BR112018075649A2 (pt) 2016-06-08 2019-04-09 Abbvie Inc. anticorpos anti-b7-h3 e conjugados de fármaco de anticorpo
IL300274A (en) 2016-06-08 2023-04-01 Abbvie Inc Antibodies against B7–H3 and conjugates of drug and antibody
EP3468993A1 (en) 2016-06-08 2019-04-17 AbbVie Inc. Anti-b7-h3 antibodies and antibody drug conjugates
FI3468586T3 (fi) 2016-06-14 2024-10-29 Xencor Inc Bispesifisiä immuuniaktivaatiota vapauttavia vasta-aineita
EA201990017A1 (ru) 2016-06-17 2019-07-31 Чугаи Сейяку Кабусики Кайся Антитела к миостатину и способы их применения
EP3475304B1 (en) 2016-06-28 2022-03-23 Xencor, Inc. Heterodimeric antibodies that bind somatostatin receptor 2
US20240018268A1 (en) 2016-07-29 2024-01-18 Juno Therapeutics, Inc. Anti-idiotypic antibodies against anti-cd19 antibodies
US11066479B2 (en) 2016-08-02 2021-07-20 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Monoclonal antibodies targeting glypican-2 (GPC2) and use thereof
JP6527643B2 (ja) 2016-08-05 2019-06-05 中外製薬株式会社 Ｉｌ−８関連疾患の治療用又は予防用組成物
EP3494139B1 (en) 2016-08-05 2022-01-12 F. Hoffmann-La Roche AG Multivalent and multiepitopic anitibodies having agonistic activity and methods of use
ES3034020T3 (en) 2016-08-15 2025-08-12 Hoffmann La Roche Chromatography method for quantifying a non-ionic surfactant in a composition comprising the non-ionic surfactant and a polypeptide
EP3500594A4 (en) 2016-08-22 2020-03-11 Cho Pharma Inc. ANTIBODIES, BINDING FRAGMENTS AND METHOD FOR USE
EP3504239B1 (en) 2016-08-25 2024-05-29 F. Hoffmann-La Roche AG Intermittent dosing of an anti-csf-1r antibody in combination with macrophage activating agent
US10793632B2 (en) 2016-08-30 2020-10-06 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
SG10201607778XA (en) 2016-09-16 2018-04-27 Chugai Pharmaceutical Co Ltd Anti-Dengue Virus Antibodies, Polypeptides Containing Variant Fc Regions, And Methods Of Use
CN116731197A (zh) 2016-09-19 2023-09-12 豪夫迈·罗氏有限公司 基于补体因子的亲和层析
JP7579056B2 (ja) 2016-10-06 2024-11-07 ジェネンテック， インコーポレイテッド がんのための治療方法及び診断方法
CA3040504A1 (en) 2016-10-14 2018-04-19 Xencor, Inc. Il15/il15ra heterodimeric fc-fusion proteins
WO2018081648A2 (en) 2016-10-29 2018-05-03 Genentech, Inc. Anti-mic antibidies and methods of use
CN110099682B (zh) 2016-11-14 2023-03-31 杭州多禧生物科技有限公司 偶联连接体，含有此连接体的细胞结合分子-药物偶联物及其制备和应用
KR20190074300A (ko) 2016-11-15 2019-06-27 제넨테크, 인크. 항-cd20/항-cd3 이중특이적 항체에 의한 치료를 위한 투약
TW201829463A (zh) 2016-11-18 2018-08-16 瑞士商赫孚孟拉羅股份公司 抗hla-g抗體及其用途
WO2018091724A1 (en) 2016-11-21 2018-05-24 Cureab Gmbh Anti-gp73 antibodies and immunoconjugates
EP3559038B1 (en) 2016-12-21 2022-12-14 The United States of America as represented by The Secretary Department of Health and Human Services Human monoclonal antibodies specific for flt3 and uses thereof
EP3558360A1 (en) 2016-12-22 2019-10-30 F. Hoffmann-La Roche AG Treatment of tumors with an anti-csf-1r antibody in combination with an anti-pd-l1 antibody after failure of anti-pd-l1/pd1 treatment
UA126574C2 (uk) 2017-02-10 2022-11-02 Дженентек, Інк. Антитіло проти триптази, його композиція та застосування
EP3589754B1 (en) 2017-03-01 2023-06-28 F. Hoffmann-La Roche AG Diagnostic and therapeutic methods for cancer
KR102769634B1 (ko) 2017-04-27 2025-02-19 테사로, 인코포레이티드 림프구 활성화 유전자-3 (lag-3)에 대한 항체 작용제 및 그의 용도
US11389480B2 (en) 2017-05-19 2022-07-19 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Human monoclonal antibody targeting TNFR2 for cancer immunotherapy
AR111963A1 (es) 2017-05-26 2019-09-04 Univ California Método y moléculas
CA3066953A1 (en) 2017-06-30 2019-01-03 Lentigen Technology, Inc. Human monoclonal antibodies specific for cd33 and methods of their use
MA49517A (fr) 2017-06-30 2020-05-06 Xencor Inc Protéines de fusion fc hétérodimères ciblées contenant il-15/il-15ra et domaines de liaison à l'antigène
WO2019005208A1 (en) 2017-06-30 2019-01-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services ANTIBODIES TO HUMAN MESOTHELIN AND USES IN ANTICANCER THERAPY
AU2018304458B2 (en) 2017-07-21 2021-12-09 Foundation Medicine, Inc. Therapeutic and diagnostic methods for cancer
WO2019078357A1 (ja) 2017-10-20 2019-04-25 中外製薬株式会社 細胞への分子の取り込みを測定する方法
US10882915B2 (en) 2017-10-24 2021-01-05 Magenta Therapeutics, Inc. Compositions and methods for the depletion of CD117+ cells
BR112020007736A2 (pt) 2017-10-30 2020-10-20 F. Hoffmann-La Roche Ag composição e método de tratamento
ES2907054T3 (es) 2017-11-01 2022-04-21 Hoffmann La Roche TriFab-Contorsbody
WO2019089969A2 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for b-cell maturation antigen
WO2019086394A1 (en) 2017-11-01 2019-05-09 F. Hoffmann-La Roche Ag The compbody - a multivalent target binder
JP7544597B2 (ja) 2017-11-06 2024-09-03 ジェネンテック， インコーポレイテッド がんの診断及び療法
US10981992B2 (en) 2017-11-08 2021-04-20 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
WO2019094637A1 (en) 2017-11-08 2019-05-16 Xencor, Inc. Bispecific and monospecific antibodies using novel anti-pd-1 sequences
EP3710589A4 (en) 2017-11-14 2021-11-10 Chugai Seiyaku Kabushiki Kaisha ANTI-C1S ANTIBODIES AND METHOD OF USING
IL316155A (en) 2017-11-29 2024-12-01 Heidelberg Pharma Res Compositions and Methods for the Depletion of CD5(PLUS) CELLS
KR102722731B1 (ko) 2017-12-19 2024-10-25 젠코어 인코포레이티드 조작된 il-2 fc 융합 단백질
US11667713B2 (en) 2017-12-28 2023-06-06 Chugai Seiyaku Kabushiki Kaisha Cytotoxicity-inducing therapeutic agent
WO2019139987A1 (en) 2018-01-09 2019-07-18 Elstar Therapeutics, Inc. Calreticulin binding constructs and engineered t cells for the treatment of diseases
US20200339686A1 (en) 2018-01-16 2020-10-29 Lakepharma, Inc. Bispecific antibody that binds cd3 and another target
US12398209B2 (en) 2018-01-22 2025-08-26 Janssen Biotech, Inc. Methods of treating cancers with antagonistic anti-PD-1 antibodies
CA3089287A1 (en) 2018-02-08 2019-08-15 Genentech, Inc. Bispecific antigen-binding molecules and methods of use
AU2019225249A1 (en) 2018-02-26 2020-09-17 Genentech, Inc. Dosing for treatment with anti-tigit and anti-PD-L1 antagonist antibodies
WO2019178362A1 (en) 2018-03-14 2019-09-19 Elstar Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
US20200040103A1 (en) 2018-03-14 2020-02-06 Genentech, Inc. Anti-klk5 antibodies and methods of use
IL277375B2 (en) 2018-03-15 2025-08-01 Chugai Pharmaceutical Co Ltd Anti-dengue virus antibodies having cross-reactivity to zika virus and methods of use
JP7104458B2 (ja) 2018-04-02 2022-07-21 上海博威生物医薬有限公司 リンパ球活性化遺伝子－３（ｌａｇ－３）結合抗体およびその使用
TW202011029A (zh) 2018-04-04 2020-03-16 美商建南德克公司 偵測及定量fgf21之方法
CN112469477A (zh) 2018-04-04 2021-03-09 Xencor股份有限公司 与成纤维细胞活化蛋白结合的异源二聚体抗体
AR114789A1 (es) 2018-04-18 2020-10-14 Hoffmann La Roche Anticuerpos anti-hla-g y uso de los mismos
JP2021521784A (ja) 2018-04-18 2021-08-30 ゼンコア インコーポレイテッド ＩＬ−１５／ＩＬ−１５ＲａＦｃ融合タンパク質とＰＤ−１抗原結合ドメインを含むＰＤ−１標的化ヘテロダイマー融合タンパク質およびそれらの使用
CA3097741A1 (en) 2018-04-18 2019-10-24 Xencor, Inc. Tim-3 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and tim-3 antigen binding domains
EP3794022A1 (en) 2018-05-14 2021-03-24 Werewolf Therapeutics, Inc. Activatable cytokine polypeptides and methods of use thereof
JP7460609B2 (ja) 2018-05-14 2024-04-02 ウェアウルフ セラピューティクス， インコーポレイテッド 活性化可能なインターロイキン－２ポリペプチド及びその使用方法
MA52777A (fr) 2018-05-24 2021-04-14 Janssen Biotech Inc Agents de liaison psma et utilisations correspondantes
PE20211091A1 (es) 2018-07-02 2021-06-14 Amgen Inc Proteina de union al antigeno anti-steap1
AU2019297451A1 (en) 2018-07-03 2021-01-28 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
EP3820903A1 (en) 2018-07-12 2021-05-19 The United States of America, as represented by the Secretary, Department of Health and Human Services Affinity matured cd22-specific monoclonal antibody and uses thereof
AU2019311077B2 (en) 2018-07-23 2025-05-29 Heidelberg Pharma Research Gmbh Use of anti-CD5 antibody drug conjugate (ADC) in allogeneic cell therapy
CA3106544A1 (en) 2018-08-08 2020-02-13 Mitchell Ho High affinity monoclonal antibodies targeting glypican-2 and uses thereof
SG10202106830VA (en) 2018-08-10 2021-08-30 Chugai Pharmaceutical Co Ltd Anti-cd137 antigen-binding molecule and utilization thereof
CA3110750A1 (en) 2018-09-10 2020-03-19 Nanjing Legend Biotech Co., Ltd. Single-domain antibodies against cd33 and constructs thereof
KR20210063330A (ko) 2018-09-19 2021-06-01 제넨테크, 인크. 방광암에 대한 치료 및 진단 방법
EP3856764A4 (en) 2018-09-27 2022-11-02 Xilio Development, Inc. MASKED CYTOKINE POLYPEPTIDES
SG11202103192RA (en) 2018-10-03 2021-04-29 Xencor Inc Il-12 heterodimeric fc-fusion proteins
KR20210079311A (ko) 2018-10-18 2021-06-29 제넨테크, 인크. 육종성 신장암에 대한 진단과 치료 방법
KR20210100668A (ko) 2018-12-06 2021-08-17 제넨테크, 인크. 항-CD79b 면역접합체, 알킬화제 및 항-CD20 항체를 포함하는 미만성 큰 B-세포 림프종의 조합 요법
TW202035442A (zh) 2018-12-20 2020-10-01 美商建南德克公司 經修飾之抗體Fc及其使用方法
WO2020127968A1 (en) 2018-12-20 2020-06-25 Marino Stephen F Protein-drug conjugate comprising a monomeric form of proteinase 3
CA3123050A1 (en) 2018-12-26 2020-07-02 City Of Hope Activatable masked anti-ctla4 binding proteins
EP3883608A1 (en) 2019-01-08 2021-09-29 The United States of America, as represented by the Secretary, Department of Health and Human Services Cross-species single domain antibodies targeting mesothelin for treating solid tumors
US12122843B2 (en) 2019-01-22 2024-10-22 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services High affinity monoclonal antibodies targeting glypican-1 and methods of use
BR112021014276A2 (pt) 2019-01-22 2021-09-28 Genentech, Inc. Anticorpos iga isolados, moléculas de fusão igg-iga isoladas, ácido nucleico isolado, célula hospedeira, método para produzir um anticorpo, para tratar um indivíduo, para aumentar a expressão de dímeros, trímeros ou tetrâmeros, para aumentar a produção de polímeros, para aumentar a produção de dímeros, para aumentar a produção de um polímero, para diminuir a produção de polímeros, para aumentar a expressão transitória de um anticorpo, para expressar dímeros de moléculas de fusão, para expressar dímeros, trímeros ou tetrâmeros, para purificar um anticorpo, para purificar um estado oligomérico de um anticorpo, composição farmacêutica e uso do anticorpo
EP3915581A4 (en) 2019-01-24 2023-03-22 Chugai Seiyaku Kabushiki Kaisha NOVEL CANCER ANTIGENS AND ANTIBODIES OF THESE ANTIGENS
CA3123303A1 (en) 2019-01-29 2020-08-06 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for receptor tyrosine kinase like orphan receptor 1 (ror1)
AU2020224681A1 (en) 2019-02-21 2021-09-16 Marengo Therapeutics, Inc. Antibody molecules that bind to NKp30 and uses thereof
GB2599228B (en) 2019-02-21 2024-02-07 Marengo Therapeutics Inc Multifunctional molecules that bind to T cell related cancer cells and uses thereof
CN113710706A (zh) 2019-02-27 2021-11-26 豪夫迈·罗氏有限公司 用于抗tigit抗体和抗cd20抗体或抗cd38抗体治疗的给药
MX2021010390A (es) 2019-03-01 2021-11-17 Xencor Inc Anticuerpos heterodimericos que se unen a enpp3 y cd3.
AU2020236015B9 (en) 2019-03-14 2024-11-28 Genentech, Inc. Treatment of cancer with HER2XCD3 bispecific antibodies in combination with anti-HER2 MAB
WO2020214963A1 (en) 2019-04-18 2020-10-22 Genentech, Inc. Antibody potency assay
TW202043291A (zh) 2019-04-19 2020-12-01 美商建南德克公司 抗mertk抗體及使用方法
AR118720A1 (es) 2019-04-19 2021-10-27 Janssen Biotech Inc Métodos para tratar el cáncer de próstata con un anticuerpo anti-psma / cd3
EP3968993A1 (en) 2019-05-14 2022-03-23 F. Hoffmann-La Roche AG Methods of using anti-cd79b immunoconjugates to treat follicular lymphoma
JP7754723B2 (ja) 2019-05-14 2025-10-15 ウェアウルフ セラピューティクス， インコーポレイテッド 分離部分及びその使用方法
CA3137649A1 (en) 2019-05-15 2020-11-19 Chugai Seiyaku Kabushiki Kaisha An antigen-binding molecule, a pharmaceutical composition, and a method
TWI870412B (zh) 2019-06-05 2025-01-21 美商建南德克公司 過載層析管柱之再生方法
JP7359864B2 (ja) 2019-07-10 2023-10-11 中外製薬株式会社 クローディン６結合分子およびその使用
US20220267452A1 (en) 2019-07-12 2022-08-25 Chugai Seiyaku Kabushiki Kaisha Anti-mutation type fgfr3 antibody and use therefor
MX2022003610A (es) 2019-09-27 2022-04-20 Genentech Inc Administracion de dosis para tratamiento con anticuerpos antagonistas anti-tigit y anti-pd-l1.
CR20220166A (es) 2019-10-18 2022-06-15 Genentech Inc Métodos para usar inmunoconjugados anti-cd79b para tratar linfoma difuso de linfocitos b grandes
EP4031250A1 (en) 2019-10-22 2022-07-27 The United States of America, as represented by the Secretary, Department of Health and Human Services High affinity nanobodies targeting b7h3 (cd276) for treating multiple solid tumors
KR20220092580A (ko) 2019-11-06 2022-07-01 제넨테크, 인크. 혈액암의 치료를 위한 진단과 치료 방법
BR112022009110A2 (pt) 2019-11-14 2022-07-26 Werewolf Therapeutics Inc Polipeptídeos de citocina ativáveis e métodos de uso destes
CN115335399A (zh) 2019-12-06 2022-11-11 朱诺治疗学股份有限公司 针对gprc5d靶结合结构域的抗独特型抗体以及相关组合物和方法
US20230028050A1 (en) 2019-12-06 2023-01-26 Juno Therapeutics, Inc. Anti-idiotypic antibodies to bcma-targeted binding domains and related compositions and methods
WO2021118968A1 (en) 2019-12-12 2021-06-17 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Antibody-drug conjugates specific for cd276 and uses thereof
AR120741A1 (es) 2019-12-13 2022-03-16 Genentech Inc Anticuerpos anti-ly6g6d y métodos de uso
UA128549C2 (uk) 2019-12-27 2024-08-07 Чугаі Сейяку Кабусікі Кайся Антитіло до ctla-4 та його застосування
JP2023509708A (ja) 2020-01-03 2023-03-09 マレンゴ・セラピューティクス，インコーポレーテッド 抗ｔｃｒ抗体分子およびその使用
CN110818795B (zh) 2020-01-10 2020-04-24 上海复宏汉霖生物技术股份有限公司 抗tigit抗体和使用方法
WO2022050954A1 (en) 2020-09-04 2022-03-10 Genentech, Inc. Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies
WO2021194481A1 (en) 2020-03-24 2021-09-30 Genentech, Inc. Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies
TWI895351B (zh) 2020-02-12 2025-09-01 日商中外製藥股份有限公司 用於癌症之治療的抗cd137抗原結合分子
PH12022552371A1 (en) 2020-03-13 2023-12-18 Genentech Inc Anti-interleukin-33 antibodies and uses thereof
WO2021188749A1 (en) 2020-03-19 2021-09-23 Genentech, Inc. Isoform-selective anti-tgf-beta antibodies and methods of use
EP4127724A1 (en) 2020-04-03 2023-02-08 Genentech, Inc. Therapeutic and diagnostic methods for cancer
BR112022021441A2 (pt) 2020-04-24 2022-12-13 Genentech Inc Métodos para tratar linfoma folicular e linfoma difuso de grandes células b e kits
EP4143345A1 (en) 2020-04-28 2023-03-08 Genentech, Inc. Methods and compositions for non-small cell lung cancer immunotherapy
WO2021231976A1 (en) 2020-05-14 2021-11-18 Xencor, Inc. Heterodimeric antibodies that bind prostate specific membrane antigen (psma) and cd3
EP4165415A1 (en) 2020-06-12 2023-04-19 Genentech, Inc. Methods and compositions for cancer immunotherapy
BR112022025801A2 (pt) 2020-06-18 2023-10-03 Hoffmann La Roche Métodos para tratar um paciente e para tratar um paciente com escc avançado, kit, anticorpo, uso de um anticorpo e uso de um antagonista de ligação
EP4179332A1 (en) 2020-07-13 2023-05-17 Genentech, Inc. Cell-based methods for predicting polypeptide immunogenicity
EP4190801A4 (en) 2020-07-29 2024-10-02 Chugai Seiyaku Kabushiki Kaisha METHOD FOR MEASURING THE PHARMACOKINETICS OF A DRUG LABELED WITH A NON-RADIOACTIVE SUBSTANCE
WO2022029660A1 (en) 2020-08-05 2022-02-10 Juno Therapeutics, Inc. Anti-idiotypic antibodies to ror1-targeted binding domains and related compositions and methods
CN115836122A (zh) 2020-08-07 2023-03-21 基因泰克公司 用于预测多肽免疫原性的基于t细胞的方法
MX2023001441A (es) 2020-08-07 2023-03-06 Genentech Inc Proteinas de fusion del ligando para flt3 y metodos de uso.
WO2022076462A1 (en) 2020-10-05 2022-04-14 Genentech, Inc. Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies
US20230391852A1 (en) 2020-10-26 2023-12-07 The U.S.A., As Represented By The Secretary, Department Of Health And Human Services Single domain antibodies targeting sars coronavirus spike protein and uses thereof
EP4236970A1 (en) 2020-10-27 2023-09-06 Vor Biopharma Inc. Compositions and methods for treating hematopoietic malignancy
IL302217A (en) 2020-11-04 2023-06-01 Genentech Inc Dosage for treatment with bispecific anti-CD20/anti-CD3 antibodies and anti-CD79B drug antibody conjugates
IL302396A (en) 2020-11-04 2023-06-01 Genentech Inc Dosage for treatment with bispecific anti-CD20/anti-CD3 antibodies
JP7716473B2 (ja) 2020-11-04 2025-07-31 ジェネンテック， インコーポレイテッド 抗ｃｄ２０／抗ｃｄ３二重特異性抗体の皮下投薬
CA3196844A1 (en) 2020-11-25 2022-06-02 Raphael Rozenfeld Tumor-specific cleavable linkers
IL303656A (en) 2020-12-17 2023-08-01 Hoffmann La Roche Anti-hla-g antibodies and use thereof
AR124681A1 (es) 2021-01-20 2023-04-26 Abbvie Inc Conjugados anticuerpo-fármaco anti-egfr
PE20240761A1 (es) 2021-01-28 2024-04-17 Janssen Biotech Inc Proteinas de union a psma y usos de estas
WO2022187270A1 (en) 2021-03-01 2022-09-09 Xilio Development, Inc. Combination of ctla4 and pd1/pdl1 antibodies for treating cancer
WO2022187272A1 (en) 2021-03-01 2022-09-09 Xilio Development, Inc. Combination of masked ctla4 and pd1/pdl1 antibodies for treating cancer
CN117157319A (zh) 2021-03-09 2023-12-01 Xencor股份有限公司 结合cd3和cldn6的异二聚抗体
KR20230154311A (ko) 2021-03-10 2023-11-07 젠코어 인코포레이티드 Cd3 및 gpc3에 결합하는 이종이량체 항체
AR125344A1 (es) 2021-04-15 2023-07-05 Chugai Pharmaceutical Co Ltd Anticuerpo anti-c1s
WO2022232612A1 (en) 2021-04-29 2022-11-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Lassa virus-specific nanobodies and methods of their use
TW202243689A (zh) 2021-04-30 2022-11-16 瑞士商赫孚孟拉羅股份公司 抗ｃｄ２０／抗ｃｄ３雙特異性抗體及抗ｃｄ７８ｂ抗體藥物結合物的組合治療之給藥
EP4329800A1 (en) 2021-04-30 2024-03-06 F. Hoffmann-La Roche AG Dosing for treatment with anti-cd20/anti-cd3 bispecific antibody
AU2022273063A1 (en) 2021-05-12 2023-11-23 Genentech, Inc. Methods of using anti-cd79b immunoconjugates to treat diffuse large b-cell lymphoma
EP4342984A4 (en) 2021-05-19 2025-04-23 Chugai Seiyaku Kabushiki Kaisha Method for predicting in vivo pharmacokinetics of molecule
JP2024521187A (ja) 2021-05-28 2024-05-28 グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッド ガンの治療のための組み合わせ療法
EP4155321A1 (en) 2021-06-04 2023-03-29 Chugai Seiyaku Kabushiki Kaisha Anti-ddr2 antibodies and uses thereof
WO2022261017A1 (en) 2021-06-09 2022-12-15 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Cross species single domain antibodies targeting pd-l1 for treating solid tumors
TWI864408B (zh) 2021-06-25 2024-12-01 日商中外製藥股份有限公司 抗ctla-4抗體的用途
JP7472405B2 (ja) 2021-06-25 2024-04-22 中外製薬株式会社 抗ｃｔｌａ－４抗体
US11807685B2 (en) 2021-08-05 2023-11-07 The Uab Research Foundation Anti-CD47 antibody and uses thereof
US20240336697A1 (en) 2021-08-07 2024-10-10 Genentech, Inc. Methods of using anti-cd79b immunoconjugates to treat diffuse large b-cell lymphoma
PE20240727A1 (es) 2021-08-27 2024-04-15 Janssen Biotech Inc Anticuerpos anti-psma y usos de estos
TW202321308A (zh) 2021-09-30 2023-06-01 美商建南德克公司 使用抗ｔｉｇｉｔ抗體、抗ｃｄ３８抗體及ｐｄ—１軸結合拮抗劑治療血液癌症的方法
EP4412713A1 (en) 2021-10-05 2024-08-14 GlaxoSmithKline Intellectual Property Development Ltd Combination therapies for treating cancer
MX2024004117A (es) 2021-10-08 2024-04-19 Chugai Pharmaceutical Co Ltd Metodo para preparar formulacion de jeringa precargada.
WO2022078524A2 (en) 2021-11-03 2022-04-21 Hangzhou Dac Biotech Co., Ltd. Specific conjugation of an antibody
JP2025501522A (ja) 2021-12-17 2025-01-22 シャンハイ・ヘンリウス・バイオテック・インコーポレイテッド 抗ｏｘ４０抗体及び使用方法
CA3240585A1 (en) 2021-12-17 2023-06-22 Wenfeng Xu Anti-ox40 antibodies, multispecific antibodies and methods of use
UY40097A (es) 2022-01-07 2023-07-14 Johnson & Johnson Entpr Innovation Inc Materiales y métodos de proteínas de unión a il-1b
MX2024011468A (es) 2022-03-23 2024-09-25 Hoffmann La Roche Tratamiento conjunto de un anticuerpo biespecifico anti-cd20/anti-cd3 y quimioterapia.
JP2025514610A (ja) 2022-03-25 2025-05-09 シャンハイ・ヘンリウス・バイオテック・インコーポレイテッド 抗ｍｓｌｎ抗体及び使用方法
CA3251490A1 (en) 2022-04-01 2023-10-05 Genentech, Inc. Hydroxypropylmethylcellulose derivatives for stabilizing polypeptides
AU2022450448A1 (en) 2022-04-01 2024-10-10 Genentech, Inc. Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies
AU2023253705A1 (en) 2022-04-13 2024-10-17 F. Hoffmann-La Roche Ag Pharmaceutical compositions of therapeutic proteins and methods of use
EP4508081A1 (en) 2022-04-13 2025-02-19 F. Hoffmann-La Roche AG Pharmaceutical compositions of anti-cd20/anti-cd3 bispecific antibodies and methods of use
US20230346862A1 (en) 2022-05-02 2023-11-02 Athanor Biosciences, Inc. Cancer eradicating - bio-nanoparticles (ce-bnp)
WO2023219613A1 (en) 2022-05-11 2023-11-16 Genentech, Inc. Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies
AU2023284422A1 (en) 2022-06-07 2024-12-19 Genentech, Inc. Method for determining the efficacy of a lung cancer treatment comprising an anti-pd-l1 antagonist and an anti-tigit antagonist antibody
AU2023295035A1 (en) 2022-06-17 2024-08-15 Genentech, Inc. Use of kosmotropes to enhance yield of an affinity chromatography purification step
AU2023305619A1 (en) 2022-07-13 2025-01-23 F. Hoffmann-La Roche Ag Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies
EP4558524A1 (en) 2022-07-19 2025-05-28 Genentech, Inc. Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies
CR20250056A (es) 2022-07-22 2025-03-19 Genentech Inc Moléculas de unión al antígeno anti-steap1 y sus usos.
CN120153254A (zh) 2022-09-01 2025-06-13 基因泰克公司 膀胱癌的治疗和诊断方法
WO2024073751A1 (en) 2022-09-29 2024-04-04 Vor Biopharma Inc. Methods and compositions for gene modification and enrichment
EP4609201A1 (en) 2022-10-25 2025-09-03 Genentech, Inc. Therapeutic and diagnostic methods for multiple myeloma
WO2024102948A1 (en) 2022-11-11 2024-05-16 Celgene Corporation Fc receptor-homolog 5 (fcrh5) specific binding molecules and bispecific t-cell engaging antibodies including same and related methods
AR131320A1 (es) 2022-12-13 2025-03-05 Juno Therapeutics Inc Receptores de antígenos quiméricos específicos para baff-r y cd19 y métodos y usos de los mismos
WO2024168312A1 (en) 2023-02-09 2024-08-15 Vor Biopharma Inc. Methods for treating hematopoietic malignancy
WO2024218345A1 (en) 2023-04-21 2024-10-24 Glaxosmithkline Intellectual Property Development Limited Cytotoxicity targeting chimeras for antibody-drug conjugates and bispecific antibodies
WO2024233341A1 (en) 2023-05-05 2024-11-14 Genentech, Inc. Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies
WO2024254455A1 (en) 2023-06-08 2024-12-12 Genentech, Inc. Macrophage signatures for diagnostic and therapeutic methods for lymphoma
WO2025019228A1 (en) 2023-07-20 2025-01-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Fully human monoclonal antibodies and chimeric antigen receptors against cd276 for the treatment of solid tumors
EP4509142A1 (en) 2023-08-16 2025-02-19 Ona Therapeutics S.L. Fgfr4 as target in cancer treatment
WO2025106474A1 (en) 2023-11-14 2025-05-22 Genentech, Inc. Therapeutic and diagnostic methods for treating cancer with anti-fcrh5/anti-cd3 bispecific antibodies
WO2025171238A1 (en) 2024-02-07 2025-08-14 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Monoclonal antibodies that bind the juxta-membrane region of mesothelin and uses thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0313873A1 (en) * 1987-10-30 1989-05-03 American Cyanamid Company Targeted forms of methyltrithio antitumor agents
EP0392384A2 (en) * 1989-04-14 1990-10-17 American Cyanamid Company Targeted forms of methyltrithio antitumor agents
US5053394A (en) * 1988-09-21 1991-10-01 American Cyanamid Company Targeted forms of methyltrithio antitumor agents
US5461068A (en) * 1993-09-29 1995-10-24 Corwood Laboratories, Inc. Imidazole derivative tincture and method of manufacture
EP0689845A2 (en) * 1994-06-03 1996-01-03 American Cyanamid Company Conjugates of methyltrithio antitumor agents and intermediates for their synthesis

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3175151D1 (en) * 1980-05-21 1986-09-25 Teijin Ltd Reactive polymer and process for the preparation thereof
SE8102193L (sv) * 1981-04-06 1982-10-07 Pharmacia Ab Terapeutiskt aktiv organisk forening och dess anvendning
CA1203164A (en) * 1982-03-09 1986-04-15 Thomas J. Mckearn Antibody conjugates
US4671958A (en) * 1982-03-09 1987-06-09 Cytogen Corporation Antibody conjugates for the delivery of compounds to target sites
US4466951A (en) * 1982-11-12 1984-08-21 University Of California Intracellular trapping of therapeutics or tracer agents
US4530835A (en) * 1983-07-08 1985-07-23 Warner-Lambert Company CL-1577 Antibiotic compounds and their production
DE3577843D1 (de) * 1984-09-10 1990-06-28 Ajinomoto Kk Biphenyldiesterverbindungen und fluessigkristallkompositionen die diese enthalten.
US4970198A (en) * 1985-10-17 1990-11-13 American Cyanamid Company Antitumor antibiotics (LL-E33288 complex)
US5431897A (en) * 1985-04-19 1995-07-11 Sloan-Kettering Institute For Cancer Research Method of imaging colorectal carcinoma lesion and composition for use therein
US5160723A (en) * 1985-04-19 1992-11-03 Sloan-Kettering Institute For Cancer Research Method of imaging colorectal carcinoma lesion and composition for use therein
FR2584293B1 (fr) * 1985-07-04 1989-03-17 Ire Celltarg Sa Anticorps utiles comme agents de pilotage et conjugues les incorporant
US5225539A (en) * 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
US5079233A (en) * 1987-01-30 1992-01-07 American Cyanamid Company N-acyl derivatives of the LL-E33288 antitumor antibiotics, composition and methods for using the same
US5037651A (en) * 1987-01-30 1991-08-06 American Cyanamid Company Dihydro derivatives of LL-E33288 antibiotics
DE3735871A1 (de) * 1987-10-23 1989-05-03 Schoeller F Jun Gmbh Co Kg Fotografisches traegermaterial fuer lichtempfindliche schichten in form eines kunststoffbeschichteten papiers oder einer kunststoffolie mit einer rueckseitenbeschichtung
EP0329184A3 (en) * 1988-02-19 1990-05-23 Neorx Corporation Antimers and antimeric conjugation
US5094849A (en) * 1988-08-08 1992-03-10 Eli Lilly And Company Cytotoxic antibody conjugates of hydrazide derivatized vinca analogs via simple organic linkers
US5028697A (en) * 1988-08-08 1991-07-02 Eli Lilly And Company Cytotoxic antibody conjugates of hydrazide derivatized methotrexate analogs via simple organic linkers
GB8928874D0 (en) * 1989-12-21 1990-02-28 Celltech Ltd Humanised antibodies
US5155210A (en) * 1990-09-11 1992-10-13 Brunswick Corporation Methods of conjugating actinomycin d
GB9120467D0 (en) * 1991-09-26 1991-11-06 Celltech Ltd Anti-hmfg antibodies and process for their production
GB2278357B (en) * 1992-12-10 1997-03-05 Celltech Ltd Humanised antibodies directed against A33 antigen

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0313873A1 (en) * 1987-10-30 1989-05-03 American Cyanamid Company Targeted forms of methyltrithio antitumor agents
US5053394A (en) * 1988-09-21 1991-10-01 American Cyanamid Company Targeted forms of methyltrithio antitumor agents
EP0392384A2 (en) * 1989-04-14 1990-10-17 American Cyanamid Company Targeted forms of methyltrithio antitumor agents
US5461068A (en) * 1993-09-29 1995-10-24 Corwood Laboratories, Inc. Imidazole derivative tincture and method of manufacture
EP0689845A2 (en) * 1994-06-03 1996-01-03 American Cyanamid Company Conjugates of methyltrithio antitumor agents and intermediates for their synthesis

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HINMAN, LOIS M. ET AL: "Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of antitumor antibiotics", CANCER RES. (1993), 53(14), 3336-42 CODEN: CNREA8;ISSN: 0008-5472, 1993, XP002014000 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8153768B2 (en) 2002-05-02 2012-04-10 Wyeth Holdings Corporation Calicheamicin derivative-carrier conjugates
US8747857B2 (en) 2002-05-02 2014-06-10 Wyeth Holdings Llc Calicheamicin derivative-carrier conjugates
US8835611B2 (en) 2002-05-02 2014-09-16 Wyeth Holdings Llc Calicheamicin derivative-carrier conjugates
US9351986B2 (en) 2002-05-02 2016-05-31 Wyeth Holdings Llc Calicheamicin derivative-carrier conjugates
EP3127553A1 (en) * 2002-05-02 2017-02-08 Wyeth Holdings LLC Calicheamicin derivative-carrier conjugates
WO2005089809A3 (en) * 2004-03-15 2006-05-04 Wyeth Corp Calicheamicin conjugation by antibody deglycosylation
WO2005089808A3 (en) * 2004-03-15 2006-08-03 Wyeth Corp Antibody calicheamicin conjugates
KR101454489B1 (ko) 2006-02-21 2014-10-27 와이어쓰 엘엘씨 칼리케아미신 유도체의 수렴형 합성 방법

Also Published As

Publication number Publication date
CN1186442A (zh) 1998-07-01
US5712374A (en) 1998-01-27
PT837698E (pt) 2001-12-28
DK0837698T3 (da) 2001-11-12
IL118565A (en) 2004-06-20
DE69614551D1 (de) 2001-09-20
CN1094063C (zh) 2002-11-13
HU221246B1 (en) 2002-09-28
IL118565A0 (en) 1996-10-16
GR3036930T3 (en) 2002-01-31
CA2223329A1 (en) 1996-12-19
CY2355B1 (en) 2004-06-04
BG63492B1 (bg) 2002-03-29
KR100499648B1 (ko) 2006-04-21
EP0837698B1 (en) 2001-08-16
JPH11508232A (ja) 1999-07-21
HUP9901351A3 (en) 2000-02-28
EP0837698A1 (en) 1998-04-29
NO975706D0 (no) 1997-12-05
KR19990022453A (ko) 1999-03-25
AR002360A1 (es) 1998-03-11
AU5742396A (en) 1996-12-30
BR9608564A (pt) 1999-07-06
ZA964614B (en) 1997-12-04
AU703862B2 (en) 1999-04-01
HK1016871A1 (en) 1999-11-12
ATE204180T1 (de) 2001-09-15
NZ307926A (en) 1999-09-29
IN182139B (enExample) 1999-01-09
ES2160818T3 (es) 2001-11-16
JP2009073832A (ja) 2009-04-09
CZ393997A3 (cs) 1998-03-18
CZ298024B6 (cs) 2007-05-30
MX9709316A (es) 1998-02-28
NO975706L (no) 1997-12-05
DE69614551T2 (de) 2002-04-11
NO324609B1 (no) 2007-11-26
TW419377B (en) 2001-01-21
BG102100A (en) 1998-08-31
HUP9901351A2 (hu) 1999-08-30

Similar Documents

Publication Publication Date Title
EP0837698B1 (en) Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
US5714586A (en) Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
US5739116A (en) Enediyne derivatives useful for the synthesis of conjugates of methyltrithio antitumor agents
AU617380B2 (en) Drug-monoclonal antibody conjugates
JP3234980B2 (ja) 新規な二官能性化合物を含むコンジュゲートの製法
RO112618B1 (ro) Medicamente conjugate continand tioeteri, procedeu de preparare a acestora, compus intermediar si compozitie farmaceutica pe baza de acesti compusi
HU206377B (en) Process for producing cytotoxic vinc-dimer conjugates and pharmaceutical compositions comprising same
HU210147B (en) Process for producing antibody-drug conjugates and pharmaceutical compositions containing them
FI95204B (fi) Menetelmä metyylitritioyhdisteiden kohdennettujen johdannaisten valmistamiseksi
KR930003333B1 (ko) 탄수화물 단위가 변형된 리보솜을 비활성화시키는 당단백질 성분을 함유하는 지속-작용성 면역독소의 제조방법
JPH0742316B2 (ja) オシド単位の酸化およびシツフ塩基の形成により変性されたリボソ−ム不活性化糖タンパク、およびこの糖タンパクを含む生体内持続性免疫毒素
JPH0780903B2 (ja) 修飾糖タンパク質、当該修飾糖タンパク質の製造方法、当該修飾糖タンパク質を含む免疫毒素および当該免疫毒素を有効成分として含む抗ガン剤組成物
CA2121990A1 (en) Antibody-drug conjugates
HK1016871B (en) Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 96194451.X

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AU BB BG BR CA CN CZ EE FI GE HU IS JP KG KP KR LK LR LT LU LV MD MG MK MN MX NO NZ PL RO RU SG SI SK TR TT UA UZ VN AM AZ BY KG KZ MD RU TJ TM

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): KE LS MW SD SZ UG AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 307926

Country of ref document: NZ

ENP Entry into the national phase

Ref document number: 2223329

Country of ref document: CA

Ref document number: 2223329

Country of ref document: CA

Kind code of ref document: A

Ref document number: 1997 500547

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 1996915718

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: PV1997-3939

Country of ref document: CZ

Ref document number: 1019970708934

Country of ref document: KR

WWP Wipo information: published in national office

Ref document number: PV1997-3939

Country of ref document: CZ

WWP Wipo information: published in national office

Ref document number: 1996915718

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1019970708934

Country of ref document: KR

WWG Wipo information: grant in national office

Ref document number: 1996915718

Country of ref document: EP

WWG Wipo information: grant in national office

Ref document number: 1019970708934

Country of ref document: KR

WWG Wipo information: grant in national office

Ref document number: PV1997-3939

Country of ref document: CZ