+

US20070087005A1 - Anti-glypican-3 antibody - Google Patents

Anti-glypican-3 antibody Download PDF

Info

Publication number
US20070087005A1
US20070087005A1 US11/251,561 US25156105A US2007087005A1 US 20070087005 A1 US20070087005 A1 US 20070087005A1 US 25156105 A US25156105 A US 25156105A US 2007087005 A1 US2007087005 A1 US 2007087005A1
Authority
US
United States
Prior art keywords
antibody
glypican
amino acid
region
acid residues
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.)
Abandoned
Application number
US11/251,561
Other languages
English (en)
Inventor
Gregory Lazar
Bassil Dahiyat
Hisafumi Okabe
Masamichi Sugimoto
Shigeyuki Iijima
Izumi Sugo
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.)
Chugai Pharmaceutical Co Ltd
Xencor Inc
Original Assignee
Chugai Pharmaceutical Co Ltd
Xencor Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chugai Pharmaceutical Co Ltd, Xencor Inc filed Critical Chugai Pharmaceutical Co Ltd
Priority to US11/251,561 priority Critical patent/US20070087005A1/en
Assigned to CHUGAI SEIYAKU KABUSHIKI KAISHA reassignment CHUGAI SEIYAKU KABUSHIKI KAISHA ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LIJIMA, SHIGEYUKI, OKABE, HISAFUMI, SUGIMOTO, MASAMICHI, SUGO, IZUMI
Assigned to XENCOR, INC. reassignment XENCOR, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DAHIYAT, BASSIL I., LAZAR, GREGORY ALAN
Priority to EP06825738.5A priority patent/EP1933872B1/fr
Priority to AU2006304100A priority patent/AU2006304100C1/en
Priority to PCT/US2006/039682 priority patent/WO2007047291A2/fr
Priority to CA2624894A priority patent/CA2624894C/fr
Priority to CN2006800379295A priority patent/CN101287492B/zh
Priority to ES06825738.5T priority patent/ES2470374T3/es
Priority to BRPI0617412A priority patent/BRPI0617412B8/pt
Priority to CN201210178007.3A priority patent/CN102850455B/zh
Priority to KR1020087009364A priority patent/KR101397858B1/ko
Priority to US12/089,957 priority patent/US9102739B2/en
Priority to JP2008535637A priority patent/JP5303274B2/ja
Publication of US20070087005A1 publication Critical patent/US20070087005A1/en
Priority to IL190472A priority patent/IL190472A/en
Priority to HK13103286.2A priority patent/HK1176076A1/xx
Priority to HK08113479.5A priority patent/HK1120427A1/xx
Priority to US14/505,932 priority patent/US10118959B2/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/303—Liver or Pancreas
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/524—CH2 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/526—CH3 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/72—Increased effector function due to an Fc-modification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]

Definitions

  • the present invention relates to an anti-glypican-3 antibody. Specifically, the present invention relates to an anti-glypican-3 antibody which has modifications in the amino acid sequence of the Fc region and exhibits enhanced ADCC activity.
  • Glypican-3 is one of a heparan sulfate proteoglycan family existing on the surface of cells, and it is suggested that GPC3 may participate in cell division in development and in growth of cancer cells, but its function is not as yet well clarified.
  • an anticancer agent utilizing the cytotoxicity activity of an antibody it is desirable that the antibody to be used has enhanced ADCC activity.
  • an anti-GPC3 antibody having enhanced cytotoxicity activity is desired for the GPC3-recognizing antibody.
  • An object of the invention is to provide an anti-GPC3 antibody having enhanced cytotoxicity as compared with conventional antibodies.
  • an anti-glypican-3 antibody with enhanced ADCC activity may be obtained by modifying the amino acid sequence in the Fc region of the antibody.
  • the present invention provides an anti-glypican-3 antibody comprising one or more amino acid substitutions introduced in the Fc region.
  • the present invention provides an anti-glypican-3 antibody in which one or more of the amino acid residues at the positions 239, 298, 326, 330 and 332 in the Fc region are substituted with other amino acid residues.
  • the present invention provides an anti-glypican-3 antibody selected from the group consisting of:
  • the present invention provides an anti-glypican-3 antibody selected from the group consisting of:
  • an anti-glypican-3 antibody having aspartic acid at the position 239, alanine at the position 298, glutamic acid at the position 326, and glutamic acid at the position 332 of the Fc region.
  • the present invention provides an anti-glypican-3 antibody selected from the group consisting of:
  • an anti-glypican-3 antibody in which the amino acid residues at the positions 239, 298, 326 and 332 of the Fc region are substituted with aspartic acid, alanine, glutamic acid, and glutamic acid, respectively.
  • the present invention provides an anticancer agent comprising the anti-glypican-3 antibody of the invention and a pharmaceutically acceptable carrier, as well as a method of treating a patient with cancer comprising administering to the patient the anticancer agent of the invention.
  • the present invention provides a method for producing an anti-glypican-3 antibody with enhanced cytotoxicity comprising:
  • the present invention provides a method for producing an anti-glypican-3 antibody with enhanced cytotoxicity comprising:
  • the present invention provides a method for producing an anti-glypican-3 antibody with enhanced cytotoxicity comprising:
  • the present invention provides an anti-glypican-3 antibody selected from the group consisting of:
  • FIG. 1 shows the scheme for preparing the Fc-modified humanized anti-glypican-3 antibody of the invention.
  • FIG. 2 shows the result of SDS-PAGE analysis of a purified Fc-modified humanized anti-glypican-3 antibody of the invention.
  • FIG. 3 shows a chromatogram of a purified Fc-modified humanized anti-glypican-3 antibody analyzed through a gel permeation column.
  • FIG. 4 shows the ADCC activity against SK-03 cells of the Fc-modified and wild-type humanized anti-glypican-3 antibodies, using human peripheral blood-derived PBMC.
  • FIG. 5 shows the ADCC activity against HepG2 cells of the Fc-modified and wild-type humanized anti-glypican-3 antibodies, using mouse marrow-derived effector cells.
  • FIG. 1 shows the structure and preparation scheme of the Fc-modified humanized anti-glypican-3 antibody of the invention.
  • the antibody is a heterotetramer of about 150,000 daltons, and comprises two same light (L) chains and two same heavy (H) chains.
  • Each light chain is bound to the heavy chain via one covalent disulfide bond, and the number of the disulfide bonds between the heavy chains varies depending on the isotype of antibody.
  • the heavy chain and the light chain each have intra-chain disulfide bridges at certain intervals.
  • Each heavy chain has a variable domain (VH) at one terminal thereof, and has many constant domains linked thereto.
  • Each light chain has a variable domain (VL) at one terminal thereof and has a constant region at the other terminal thereof.
  • the constant region of the light chain is in parallel to the first constant region of the heavy chain, and the variable region of the light chain is in parallel to the variable region of the heavy chain. It is believed that specific amino acid residues form an interface of the variable domain of the light chain and the heavy chain (Clothia et al., J. Mol. Biol., 186:651-666 (1985); Novotny and Haber, Proc. Natl. Acad. Sci. USA 82:4592-4596 (1985), all hereby incorporated by reference in its entirety).
  • the light chain of a vertebrate-derived antibody may be classified into two different types, referred to as kappa ( ⁇ ) and lambda ( ⁇ ), based on the amino acid sequence of the constant region thereof.
  • the antibody may be classified into different classes based on the amino acid sequence of the constant domain of the heavy chain thereof.
  • the antibody includes at least five main classes: IgA, IgD, IgE, IgG and IgM, and some of them may be classified into subclasses (isotypes), e.g., IgG-1, IgG-2, IgG-3 and IgG-4; IgA-1 and IgA-2.
  • the heavy chain constant domains of different classes are referred to as ⁇ , ⁇ , ⁇ , ⁇ and ⁇ .
  • the subunit structure and the three-dimensional structure of immunoglobulin of each class are known in the art. It is also known that there exist allotypes in the sequence of the Fc region of IgG-1, for example, Glm(1), nGlm(1), Glm(2), Glm(3), nGlm(17), etc. (M. S. Schanfield and E. van Loghem, “Human Immunoglobulin Allotypes” Handbook of Experimental Immunology, Vol. 3, ch94, pp1-18, Blackwell Scientific Publishers. Oxford, U.K. 1986, 4th Edition, hereby incorporated by reference in its entirety).
  • Fc region means a region of an Fc fragment of an antibody molecule, comprising a part of hinge, CH2 and CH3 domains and having a molecular weight of about 50,000.
  • a human IgG heavy chain Fc region is from the 225th threonine to the C-terminal, in the case that the molecule is digested with papain (Burton, D. R. 1985. Immunoglobulin G: functional sites. Mol. Immunol. 22:161-206, hereby incorporated by reference in its entirety).
  • the numbering of the amino acid position as used herein refers to the method of “EU index” by Kabat et al (Kabat EA et al., 1991, Sequence of Proteins of Immunological Interest. 5th Ed. NIH, hereby incorporated by reference in its entirety).
  • the Fc region binds to an Fc receptor (FcR) present on the cell surface of effector cells, such as macrophages and NK cells.
  • Fc receptor participates in antibody-dependent cytotoxicity (ADCC), anaphylaxis reaction, id reaction, etc.
  • ADCC antibody-dependent cytotoxicity
  • the type of Fc receptor varies, depending on the subtype of immunoglobulin. For example, Fc receptor of IgG is Fc ⁇ receptor; Fc receptor of IgE is Fc ⁇ receptor; and Fc receptor of IgA is Fc ⁇ receptor.
  • the CH2-CH3 domain consists of the CH2 domain and the CH3 domain.
  • the CH2-CH3 domain of a human IgG heavy chain is from the 233th alanine to the C-terminal.
  • the antibody of the invention is an Fc-modified antibody in which the amino acid sequence in the Fc region is modified.
  • “Modification” or “site-specific mutagenesis (mutagenesis)” used in the invention includes substituting an original (unmodified) amino acid residue with any other amino acid residue, deletion of an original amino acid residue, and addition of an additional amino acid residue, but preferably indicates substitution of an original amino acid residue with any other amino acid residue.
  • the original (unmodified) amino acid sequence as referred to herein is usually a natural Fc region sequence.
  • “modification” and “mutagenesis” of amino acid residue are used in the same meaning.
  • modification of amino acid residues may be effected by mutating the DNA that codes for the antibody.
  • mutation of DNA means that DNA is mutated in such a manner that it may correspond to the amino acid residue to be modified. More specifically, it means that the DNA coding for the original amino acid residue is mutated to DNA coding for the amino acid residue to be modified. In general, it means genetic engineering or mutagenesis treatment for insertion, deletion or substitution of at least one nucleotide of the original DNA so as to give a codon that codes for the intended amino acid residue. Specifically, the codon that codes for the original amino acid residue is substituted with the codon that codes for the amino acid residue to be modified.
  • the number of the amino acid residues in the Fc region to be modified in the invention is not specifically limited, but one or more (for example, from 1 to 30, or 2, 3, 4 or 5) amino acid residues may be modified.
  • amino acid residues at the positions 239, 298, 326, 330 and 332 in the Fc region are substituted with other amino acid residues.
  • any amino acid residues of the Fc region may be substituted with those of any allotypes of IgG1, for example, with the amino acid residues of Glm(1) and nGlm(1).
  • the anti-glypican-3 antibody of the invention is not specifically limited so far as it binds to glypican-3, but preferably, the antibody specifically binds to glypican-3.
  • the gene sequence and the amino acid sequence of glypican-3 are known (Lage, H. et al., Gene 188 (1997), 151-156, hereby incorporated by reference in its entirety).
  • the anti-glypican-3 antibody of the invention is preferably IgG, more preferably IgG1.
  • the anti-glypican-3 antibody of the invention containing modified Fc region exhibits enhanced cytotoxicity activity as compared with the anti-glypican-3 antibody having a natural or wild type Fc region.
  • Cytotoxicity activity includes, for example, antibody-dependent cell-mediated cytotoxicity (ADCC) activity, and complement-dependent cytotoxicity (CDC) activity.
  • ADCC antibody-dependent cell-mediated cytotoxicity
  • CDC complement-dependent cytotoxicity
  • the CDC activity means a cytotoxicity activity caused by a complement system
  • the ADCC activity means that, when a specific antibody adheres to the cell surface antigen of a target cell, then an Fc ⁇ receptor-having cell (e.g., immunocyte) binds to the Fc region via an Fc ⁇ receptor to thereby impair the target cell.
  • Determination of whether an antibody has ADCC activity or CDC activity may be carried out according to a known method (for example, see Current Protocols in Immunology, Chapter 7, Immunologic Studies in Humans, Editor, John E. Coligan et al., John Wiley & Sons, Inc. (1993), hereby incorporated by reference in its entirety).
  • the ADCC activity may be determined by mixing an effector cell, a target cell and an anti-glypican-3 antibody, then analyzing it for the degree of ADCC activity.
  • the effector cell may include, for example, a mouse spleen cell, or a monocyte isolated from marrow or human peripheral blood.
  • the target cell may include an established human cell line such as human hepatocyte cell line HuH-7.
  • An anti-glypican-3 antibody is added to the target cell previously labeled with 51Cr and incubated, then an effector cell is added in a suitable ratio to the target cell. After incubation, the supernatant is collected and analyzed for radioactivity to determine the ADCC activity of the antibody.
  • the CDC activity may be determined by mixing the above-mentioned labeled target cell and an anti-glypican-3 antibody, adding a complement to the mixture and incubating, and then analyzing the supernatant for radioactivity.
  • antibody as referred to herein is used in the broadest sense of the word, indicating any and every antibody that includes monoclonal antibody (including full-length monoclonal antibody), polyclonal antibody, antibody mutant, antibody fragment, poly-specific antibody (e.g., bispecific antibody), chimera antibody, humanized antibody and others, so far as it shows the desired biological activity.
  • Antibody and immunoglobulin are proteins having the same structure characteristics, and the antibody in the invention includes immunoglobulin.
  • the term “monoclonal antibody” as referred to herein indicates an antibody obtained from a group of substantially homogeneous antibodies, or that is, an antibody group in which all individual antibodies are uniform except minor mutants that may occur in nature.
  • a monoclonal antibody is highly specific and generally acts on a single antigen site. Further, as compared with conventional polyclonal antibody preparations that typically include different antibodies to different epitopes, each monoclonal antibody is directed to a single epitope on an antigen. In addition to the specificity thereof, a monoclonal antibody has another advantage in that it is synthesized through culture of a hybridoma which is not contaminated with any other antibodies.
  • the modifier “monoclonal” suggests the nature of the antibody obtained from a group of substantially uniform antibodies, and it does not require that the antibody be produced by a specific method.
  • the monoclonal antibody for use in the invention may be produced, for example, according to a hybridoma method (Kohler and Milstein, Nature 256:495 (1975), hereby incorporated by reference in its entirety), or a recombination method (U.S. Pat. No. 4,816,567, hereby incorporated by reference in its entirety).
  • the monoclonal antibody for use in the invention may also be isolated from a phage antibody library (Clackson et al., Nature 352:624-628 (1991); Marks et al., J. Mol. Biol., 222:581-597 (1991), all hereby incorporated by reference in its entirety).
  • antibody fragment indicates a portion of a full-length antibody.
  • the antibody fragment for use in the invention is preferably an antibody fragment that maintains an antibody-binding activity and maintains a cytotoxicity activity of the full-length antibody.
  • a multi-specific antibody is an antibody having specificity to at least two different antigens.
  • this type of molecule may bind to two antigens (that is, bispecific antibody), but in this description, the “multi-specific antibody” includes antibodies having specificity to more than two (for example, three) antigens.
  • the multi-specific antibody may be a full-length antibody or a fragment of such an antibody.
  • the bispecific antibody may recognize two different antigens or may recognize different epitopes of one antigen.
  • one may recognize a cytotoxic substance.
  • the antibody of the present invention may also be a chimera antibody or a humanized antibody.
  • a chimera antibody comprises a variable region derived from an antibody of a non-human mammal, and a constant region derived from a human antibody.
  • humanized antibody comprises a complementarity-determining region derived from a non-human mammal, and a framework region and a constant region derived from a human antibody.
  • the origin of the variable region in a chimera antibody, and the origin of a CDR in a humanized antibody are not specifically limited, but may be derived from any animals.
  • any sequences derived from mouse antibody, rat antibody, rabbit antibody, or camel antibody may be used (Cook W J et al., Protein Eng. 1996 July 9(7):623-8; Tsurushita N et al., J Immunol Methods. 2004 December 295(1-2):9-19; Sato K et al, Mol Immunol. 1994 Apr. 31(5):371-81; Preparation of genetically engineered monoclonal antibodies for human immunotherapy. Hum Antibodies Hybridomas. 1992 July 3(3):137-45; Genetically engineered antibodies: progress and prospects. Crit Rev Immunol. 1992; 12(3-4):125-68, all hereby incorporated by reference in its entirety).
  • a chimera antibody and a humanized antibody those derived from a human antibody may be used.
  • C ⁇ 1, C ⁇ 2, C ⁇ 3, C ⁇ 4 may be used for the H-chain
  • C ⁇ and C ⁇ may be used for the L-chain.
  • Chimera antibody is an antibody constructed by combining sequences derived from different animals, and for example, it is an antibody comprising the heavy chain and light chain variable regions of a mouse antibody and the heavy chain and light chain constant regions of a human antibody.
  • Such a chimera antibody may be constructed in any known methods. For example, a DNA coding for a mouse antibody variable region and a DNA coding for a human antibody constant region are ligated, then inserted into an expression vector, and introduced into a host to produce the intended antibody.
  • a humanized antibody also referred to as a reshaped human antibody, is constructed by transplanting a complementarity-determining region (CDR) of an antibody of a mammal except human, for example, a mouse antibody into the complementarity-determining region of a human antibody.
  • CDR complementarity-determining region
  • a general genetic recombination method for making a humanized antibody is known in the art (see EP 125023; WO96/02576, hereby incorporated by reference in its entirety).
  • a DNA sequence designed so as to ligate CDR of a mouse antibody with the framework region (FR) of a human antibody may be synthesized through PCR using, as a primer, several oligonucleotides constructed so as to have portions overlapping with the terminal region of both CDR and FR (see the method described in WO98/13388, hereby incorporated by reference in its entirety).
  • the framework region of a human antibody to be ligated with CDR is so selected that the complementarity-determining region may form a good antigen-binding site.
  • the amino acids in the framework region of the variable region of the antibody may be substituted in order that the complementarity-determining region of the reshaped human antibody may form a suitable antigen-binding site (Sato, K. et al., Cancer Res. (1993) 53, 851-856, hereby incorporated by reference in its entirety).
  • those antibodies are also included in the antibody of the invention which have mutation in one or more amino acids in regions other than the specified sites in the Fc region mentioned above or CDR region, and which is functionally equivalent to the antibody of the invention.
  • a method of introducing a mutation into the polypeptide is well known to those skilled in the art.
  • those skilled in the art may introduce a mutation to the antibody of the invention according to a site-specific mutagenesis or the like to thereby prepare an antibody functionally equivalent to that antibody.
  • Amino acid mutation may also occur spontaneously.
  • amino acid side chains include hydrophobic amino acids (A, I, L, M, F, P, W, Y, V), hydrophilic amino acids (R, D, N, C, E, Q, G, H, K, S, T), aliphatic side chain-having amino acids (G, A, V, L, I, P), hydroxyl group-containing side chain-having amino acids (S, T, Y), sulfur atom-containing side chain-having amino acids (C, M), carboxylic acid and amido-containing side chain-having amino acids (D, N, E, Q), base-containing side chain-having amino acids (R, K, H), aromatic side chain-having amino acids (H, F, Y, W) (the parenthesized alphabets are the one-letter code for amino acids).
  • hydrophobic amino acids A, I, L, M, F, P, W, Y, V
  • hydrophilic amino acids R, D, N, C, E, Q, G, H, K, S, T
  • the antibody for use in the invention may be a conjugated antibody bound with a various types of molecules, such as non-peptidic polymers such as polyethylene glycol (PEG), radioactive substances and toxins.
  • a conjugated antibody may be obtained through chemical modification of the antibody.
  • the method of chemical modification has been established in the art.
  • the antibody of the invention may include these conjugated antibodies (D. J. King., Applications and Engineering of Monoclonal antibodies., 1998 T. J. International Ltd, Monoclonal Antibody-Based Therapy of Cancer., 1998 Marcel Dekker Inc; Chari et al., Cancer Res., 1992 Vol 152:127; Liu et al., Proc Natl Acad Sci USA., 1996 Vol 93:8681, all hereby incorporated by reference in its entirety).
  • the antibody of the invention may be produced according to a method known to those skilled in the art. Specifically, DNA coding for the intended antibody is inserted into an expression vector. In this step, DNA is inserted into an expression vector in such a manner that it could be expressed under control of an expression control region, for example, an enhancer and a promoter. Next, a host cell is transformed with the expression vector and the antibody is expressed in the host cell. In this process, a combination of a suitable host and a suitable expression vector may be used.
  • vectors examples include M13 vector, pUC vector, pBR322, pBluescript, pCR-Script.
  • pGEM-T For subcloning and separation of cDNA, for example, pGEM-T, pDIRECT and pT7 may also be used.
  • Expression vectors are especially useful for the purpose of antibody production.
  • E. coli such as JM109, DH5 ⁇ , HB101 or XL1-Blue
  • the expression vector must indispensably have a promoter that drives efficient expression of the vector in E. coli , for example, lacZ promoter (Ward et al., Nature (1989) 341, 544-546; FASEB J. (1992) 6, 2422-2427, hereby incorporated by reference in its entirety), araB promoter (Better et al., Science (1988) 240, 1041-1043, hereby incorporated by reference in its entirety) or T7 promoter.
  • lacZ promoter Ward et al., Nature (1989) 341, 544-546; FASEB J. (1992) 6, 2422-2427, hereby incorporated by reference in its entirety
  • araB promoter Better et al., Science (1988) 240, 1041-1043, hereby incorporated by reference in its entirety
  • T7 promoter for example,
  • the vector of this type also includes pGEX-5X-1 (Pharmacia), QIA express system (QIAGEN), pEGFP, and pET (in this case, the host is preferably a T7 RNA polymerase-expressing BL21).
  • the vector may include a signal sequence for polypeptide secretion.
  • a signal sequence for polypeptide secretion for example, pelB signal sequence (Lei, S. P. et al., Bacteriol. (1987) 169, 4397, hereby incorporated by reference in its entirety) may be used for production in periplasm of E. coli .
  • the introduction of the vector into a host cell may be effected, for example, according to a calcium chloride method or an electroporation method.
  • the vector used for polypeptide production in the invention includes, for example, mammal-derived expression vectors (e.g., pcDNA3 (Invitrogen), pEGF-BOS (Nucleic acids, Res., 1990, 18(17), p.
  • mammal-derived expression vectors e.g., pcDNA3 (Invitrogen), pEGF-BOS (Nucleic acids, Res., 1990, 18(17), p.
  • pEF Bac-toBAC baculovairus expression system (GIBCO BRL), pBacPAK8)
  • insect cell-derived expression vectors e.g., Bac-toBAC baculovairus expression system (GIBCO BRL), pBacPAK8
  • vegetable-derived expression vectors e.g., pMH1, pMH2
  • animal virus-derived expression vectors e.g., pHSV, pMV, pAdexLcw
  • retrovirus-derived expression vectors e.g., pZIPneo
  • yeast-derived expression vectors e.g., Pichia Expression Kit (Invitrogen), pNV11, SP-Q01
  • Bacillus subtilis -derived expression vectors e.g., pPL608, pKTH50.
  • the vector For expression in animal cells such as CHO cells, COS cells or NIH3T3 cells, the vector must indispensably have a promoter necessary for intracellular expression, for example, SV40 promoter (Mulligan et al., Nature (1979) 277, 108, hereby incorporated by reference in its entirety), MMTV-LTR promoter, EF1 ⁇ promoter (Mizushima et al., Nucleic Acids Res. (1990) 18, 5322, hereby incorporated by reference in its entirety), CAG promoter (Gene (1991) 108, 193, hereby incorporated by reference in its entirety), CMV promoter.
  • SV40 promoter Mulligan et al., Nature (1979) 277, 108, hereby incorporated by reference in its entirety
  • MMTV-LTR promoter EF1 ⁇ promoter
  • CAG promoter Gene (1991) 108, 193, hereby incorporated by reference in its entirety
  • CMV promoter CMV promoter
  • the vector has a gene for screening of the transformed cells (e.g., drug-resistant gene capable of being differentiated by drug (e.g., neomycin, G418)).
  • the vector having such characteristics includes, for example, pMAM, pDR2, pBK-RSV, pBK-CMV, pOPRSV, pOP13.
  • a vector having a complementary DHFR gene (e.g., PCHOI) is introduced into CHO cells deficient in the nucleic acid synthetic pathway to complement the deficiency and is amplifyed with methotrexate (MTX).
  • MTX methotrexate
  • COS cells having an SV40T antigen-expressing gene on the chromosome is transformed with a vector having SV40 replication origin (e.g., pcD).
  • the replication origin may also be derived from polyoma virus, adeno virus, bovine polyoma virus (BPV), etc.
  • the expression vector may contain a selected marker, such as aminoglycoside transferase (APH) gene, thymidine kinase (TK) gene, E. coli xanthine-guanine phosphoribosyl transferase (Ecogpt) gene, dihydrofolate reductase (dhfr) gene.
  • APH aminoglycoside transferase
  • TK thymidine kinase
  • Ecogpt E. coli xanthine-guanine phosphoribosyl transferase
  • dhfr dihydrofolate reductase
  • the invention also relates to a pharmaceutical composition containing the antibody of the invention. Since the antibody of the invention exhibits enhanced cytotoxicity activity, it is suitable for use in pharmaceutical compositions, and in particular, it is useful as an anticancer agent. Since it has been shown that an anti-glypican-3 antibody has a cytotoxicity against a hepatoma-derived cell line (e.g. WO03/00883, hereby incorporated by reference in its entirety), the antibody of the invention is particularly useful as a drug for treating hepatic cancer. When the antibody of the invention is used in pharmaceutical compositions, it is preferably a humanized antibody in view of the antigenicity to humans.
  • the pharmaceutical composition of the invention may contain a pharmaceutically-acceptable carrier.
  • the pharmaceutically-acceptable carrier includes, for example, sterile water, physiological saline, stabilizer, excipient, antioxidant (e.g., ascorbic acid), buffer (e.g., phosphoric acid, citric acid, other organic acids), preservative, surfactant (e.g., PEG, Tween), chelating agent (e.g., EDTA), or binder.
  • composition of the invention may further contain any other low-molecular polypeptides; proteins such as serum albumin, gelatin, or immunoglobulin; amino acids such as glycine, glutamine, asparagine, arginine, lysine; saccharides such as polysaccharides, monosaccharides; carbohydrates; sugar alcohols such as mannitol, sorbitol.
  • proteins such as serum albumin, gelatin, or immunoglobulin
  • amino acids such as glycine, glutamine, asparagine, arginine, lysine
  • saccharides such as polysaccharides, monosaccharides
  • carbohydrates sugar alcohols such as mannitol, sorbitol.
  • composition When the composition is prepared as an aqueous solution for injection, it may be combined with an isotonic solution containing, for example, physiological saline, glucose or any other auxiliary agent, such as D-sorbitol, D-mannose, D-mannitol, sodium chloride, and with a suitable dissolution aid such as alcohol (e.g., ethanol), polyalcohol (e.g., propylene glycol, PEG), nonionic surfactant (e.g., Polysorbate 80, HCO-50).
  • a suitable dissolution aid such as alcohol (e.g., ethanol), polyalcohol (e.g., propylene glycol, PEG), nonionic surfactant (e.g., Polysorbate 80, HCO-50).
  • alcohol e.g., ethanol
  • polyalcohol e.g., propylene glycol, PEG
  • nonionic surfactant e.g., Polysorbate 80, HCO-50
  • the composition may be encapsulated into microcapsules (microcapsules of hydroxymethyl cellulose, gelatin, poly(methyl methacrylate), etc.), or may be formed into colloid drug delivery systems (e.g., liposomes, albumin microspheres, microemulsions, nanoparticles, nanocapsules) (see Remington's Pharmaceutical Science, 16th edition, Oslo Ed., 1980, hereby incorporated by reference in its entirety).
  • a method of formulating slow-release drugs is known and may be applicable to the invention (Langer et al., J. Biomed. Mater. Res., 1981, 15:167-277; Langer, Chem. Tech., 1982, 12:98-105; U.S. Pat. No. 3,773,919; EP 58,481; Sidman et al., Biopolymers 1983, 22:547-556; EP 133,988).
  • composition may be administered to patients either orally or parenterally, but preferably parenterally.
  • shape (preparation form) of the pharmaceutical composition of the invention is not specifically limited but includes, for example, injections, transnasal preparations, transpulmonary preparations, percutaneous preparations, freeze-dried preparations, solutions. Preferred are freeze-dried preparations.
  • Freeze-drying may be effected in any method well known to those skilled in the art (Pharm. Biotechnol., 2002, 13, 109-133; Int. J. Pharm., 2000, 203(1-2), 1-60; Pharm. Res., 1997, 14(8), 969-975, all hereby incorporated by reference in its entirety).
  • a solution of the composition is suitably aliquoted into freeze-drying vials or the like vessels, and put in a freezer or a freeze-dryer, or dipped in a coolant such as acetone/dry ice and liquid nitrogen.
  • the antibody preparation When the antibody preparation is formed into a high-concentration solution preparation, it may be prepared according to a method well known to those skilled in the art.
  • a membrane concentration method using a TFF membrane may be employed as described in J. Pharm. Sci., 2004, 93(6), 1390-1402, hereby incorporated by reference in its entirety.
  • the formulation for injection may be systemically or topically administered in a mode of, for example, intravenous injection, intramuscular injection, intraperitoneal injection or subcutaneous injection.
  • the administration method for it may be suitably selected.
  • the dose may be selected, for example, from a range of from 0.0001 mg/kg of body weight to 1000 mg/kg of body weight for a unit dose.
  • the dose may be selected from a range of from 0.001 to 100000 mg/body.
  • the invention should not be limited to the dose and the administration method as above.
  • FIG. 1 shows the structure and preparation strategy of the Fc-modified antibodies of the invention.
  • Fc-mutation cassettes for constructing five types of Fc-modified antibodies named V22, V209, V212, V922 and V1608 were produced according to a PCR-Walking method. Specifically, primers commonF1 and commonR1 were used for V22, V209 and V922; and primers 212-F1 and 212-F1 were used for V212 and V1608.
  • a first-stage PCR was carried out in a PCR reaction solution mentioned below:
  • One microliter of the first stage-amplified product was taken out and used in the next, second-stage PCR reaction.
  • primers CommonF2 and 212-R2 were used for V22 and V212; primers CommonF2 and 209-R2 were used for V209; primers CommonF2 and 922-R2 were used for V922; and primers CommonF2 and 1608-R2 were used for V1608.
  • the second-stage PCR was carried out in a PCR reaction solution mentioned below:
  • One microliter of the second stage-amplified product was taken out and used in the next, third-stage PCR reaction.
  • primers CommonF3 and CommonR3 were used for V22, V209, V212, V922 and V1608, and the third-stage PCR was carried out in a PCR reaction solution mentioned below.
  • Forward primer 212-F1 (SEQ ID NO:1) agttcaactggtacgtggacggcgtggaggtgcataatgccaagacaaag ccgcgggaggagcagtacaacgccacgtaccgtgtggtcagcgtcc Forward primer: commonF2 (SEQ ID NO:2) tctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacgaa gaccctgaggtcaagttcaactggtacgtggacggcgtggaggagg Forward primer: commonF3 (SEQ ID NO:3) gcacctgagctcctggggggaccggacgtcttcccccccaaaacc caaggacaccctcatgat
  • a vector for expressing the Fc-modified anti-GPC3 antibody of the invention was constructed based on a gene coding for a humanized anti-glypican-3 antibody previously prepared by the inventors (H-chain, SEQ ID NO: 10; L-chain, SEQ ID NO: 11), which is referred to as “wild-type” in the following Examples.
  • H-chain variable region and L-chain variable region of the wild-type humanized anti-GPC3 antibody are shown in SEQ ID NO: 21 (ver.k) and SEQ ID NO: 22 (ver.a), respectively.
  • the CDR sequences of the wild-type humanized anti-GPC3 antibody are shown below.
  • H-chain CDR1 DYEMH SEQ ID NO:23)
  • CDR2 ALDPKTGDTAYSQKFKG SEQ ID NO:24
  • CDR3 FYSYTY SEQ ID NO:25
  • L-chain CDR1 RSSQSLVHSNGNTYLH SEQ ID NO:26
  • CDR2 KVSNRFS SEQ ID NO:27
  • CDR3 SQNTHVPPT SEQ ID NO:28
  • the fragment obtained was introduced into the SmaI site of pBluescriptSK + (pB-Sacless), in which the SacI site had been previously filled up with a DNA blunting kit (Takara Bio), and its sequence was confirmed (pB-GPCSacmt).
  • pB-GPCSacmtC an SmaI-BamHI fragment of about 290 bp, corresponding to the C-terminal sequence of anti-human GPC3 antibody H-chain
  • the Fc-mutation cassette of V22, V209, V212, V922 or V1608 produced in Example 1-1 was introduced into the SacI-SmaI site of pB-GPCSacmtC, and the sequence of pB-GPCSacmtC was confirmed. Further, for completing construction of the mutated H-chain, an EcoRI-NheI fragment of about 415 bp of the GPC3 antibody H-chain gene shown by SEQ ID NO:10 was ligated with it to obtain a gene coding for Fc-mutated H-chain.
  • the resultant gene coding for a mutated H-chain was cleaved with EcoRI-NotI, and introduced into the corresponding site of an animal cell expression vector pCXND3 (pC-aGPCh).
  • pCXND3 pC-aGPCh
  • a fragment of about 3.1 kb, containing an anti-GPC3 antibody L-chain gene shown by SEQ ID NO:13 and a promoter region was cleaved with HindIII, and ligated with the corresponding site of pC-aGPCh to obtain an anti-GPC3 antibody expression vector (pC-aGPCh1).
  • the vector pC-aGPCh1 to V22, V209, V212, V922 and V1608 was designated as pC-aGPCh1(22), pC-aGPCh1(209), pC-aGPCh1(212), pC-aGPCh1(922) and pC-aGPCh1(1608), respectively.
  • V22 SEQ ID NO: 29
  • V209 SEQ ID NO: 30
  • V212 SEQ ID NO: 31
  • V922 SEQ ID NO: 32
  • V1608 SEQ ID NO: 33
  • V22 CH2-CH3 domain SEQ ID NO: 34
  • V209 CH2-CH3 domain SEQ ID NO: 35
  • V212 CH2-CH3 domain SEQ ID NO: 36
  • V922 CH2-CH3 domain SEQ ID NO: 37
  • V1608 CH2-CH3 domain SEQ ID NO: 38
  • nGlm(1) allotype of V209 For obtaining an nGlm(1) allotype of V209, a Glm(1) allotype thereof, a cassette for nGlm(1) allotype was formed. Specifically, using forward primer HerSmaF and reverse primer HerNotR shown by SEQ ID NO: 14 and NO:15, and using, as a template, the anti-GPC3 antibody H-chain gene shown by SEQ ID NO:10 and produced in Example 1-2, PCR was carried out under the condition mentioned below.
  • the fragment obtained was subcloned into pBluescriptSK + (pBher), and its sequence was confirmed.
  • an SmaI-NotI fragment of about 290 bp was cut out from pC-aGPCh1(209) described in Example 1-2.
  • Smal-NotI fragment was cut out from pBher in the same manner, and the fragment of about 290 bp was introduced into the corresponding site of pC-aGPCh1(209) for substitution to obtain a nGlm(1) allotype expression vector (pC-aGPCh1(209Her)).
  • the cells were screened in CHO-S-SFMII medium (Invitrogen) containing 400 ⁇ g/ml of geneticin. Selected cells were inoculated into a CHO-S-SFMII medium containing 400 ⁇ g/ml geneticin in a 96-well plate at 0.4 cells/100 ⁇ l/well, and the cells were cloned according to a limiting dilution method. The culture supernatant was analyzed with BIACORE 3000. The antigen was quantified using a chip with fused protein GST-GPC3 (antigen GST and human glypican-3 shown by SEQ ID NO:16) immobilized thereon, and high-expression cells were selected. Amino acid sequence of GPC3 peptide (SEQ ID NO:16) AELAYDLDVDDAPGNSQQATPKDNEISTFHNLGNVHSPLK
  • the culture supernatant of CHO cells expressing Fc-modified humanized glypican antibody was applied to an rProtein A Sepharose Fast Flow column equilibrated with 150 mM NaCl-containing 10 mM citrate-phosphate buffer (pH 7.5). The column was washed with the same buffer, 1 M NaCl-containing 10 mM citrate-phosphate buffer (pH 7.5), then 10 mM citrate-phosphate buffer (pH 7.5), and the protein adsorbed to the column was eluted out with 20 mM acetic acid.
  • FIG. 2 shows the result of SDS-PAGE (polyacrylamide gel electrophoresis) of a purified Fc-modified humanized anti-glypican antibody of the invention in a known method (Nature, 227, 680, 1970, hereby incorporated by reference in its entirety) to analyze the molecular weight and the degree of purification of the antibody.
  • Each purified Fc-modified humanized anti-glypican antibody provided a single band at a molecular weight of about 150 kDa under a non-reducing condition and provided two bands at about 50 kDa and about 25 kDa under a reducing condition.
  • FIG. 3 shows a chromatogram of a purified Fc-modified humanized anti-glypican-3 antibody analyzed through a gel permeation column (Superdex 200 PC3.2/30, by GE Amersham Biosciences).
  • a full-length cDNA coding for human GPC3 was amplified through PCR using Advantage2 kit (CLONETECH) and, as a template, 1st strand cDNA having been prepared from colon cancer cell line Caco2 in an ordinary manner.
  • the PCR amplified product was inserted into a TA vector pGEM-Teasy by the use of pGEM-T Easy Vector System I (Promega). The sequence of the product was confirmed using ABI3100 DNA sequencer. In this way, cDNA coding for the full length of human GPC3 was isolated.
  • the nucleotide sequence of human GPC3 gene is shown in SEQ ID NO:19, and the amino acid sequence of human GPC3 protein is shown in SEQ ID NO:20.
  • a human hepatic cell line capable of expressing a full-length GPC3 was established.
  • human GPC3 in each cell clone was determined by flow cytometry using chimera GC33 antibody and FITC-labeled goat anti-human IgG antibody (ICN) to obtain a stable expression cell line SK-03 was obtained.
  • Heparin-added peripheral blood was collected from a healthy person, diluted 2-fold with PBS( ⁇ ) and overlaid on Ficoll-PaqueTM PLUS (Amersham). After centrifugation (500 ⁇ g, 30 minutes, 20° C.), the interlayer of a monocyte fraction was collected. The monocytes were washed three times and suspended in 10% FBS/RPMI to prepare a human PBMC solution.
  • SK-03 cells were maintained in D-MEM medium (SIGMA) containing 1 mg/ml of geneticin and 10% FBS (ThermoTrace). The cells were peeled from the dish using Cell Dissociation Buffer (Invitrogen), and transferred to each well of a 96-well U-bottomed plate (Falcon) at 1 ⁇ 10 4 cells/well, and incubated for 1 day. After the incubation, 5.55 MBq of Chromium-51 was added and the cells were further incubated in a 5% CO 2 incubator at 37° C. for 4 hours. The cells were washed once with the medium, and suspended in 50 ⁇ l of 10% FBS/RPMI1640 medium to prepare target cells.
  • SIGMA D-MEM medium
  • FBS ThermoTrace
  • the experiment was carried out in triplicate, and the mean value of the ADCC activity (%) of the sample was calculated.
  • the results are shown in FIG. 4 .
  • the Fc-modified humanized anti-glypican antibodies V22, V209, V922, V1608 and V209(nGlm(1)) all had enhanced ADCC activity compared to the wild-type antibody (WT). Of those, the activity of V22 was lower than that of the others, but there was found little difference in the activity between V209, V922, V1608 and V209(nGlm(1)).
  • Marrow cells were collected from the thigh bone of an SCID mouse (from Nippon Clea, male, 10 weeks old), and suspended in 10% FBS/RPMI1640 medium at a density of 5 ⁇ 10 5 cells/ml.
  • Mouse GM-CSF (Pepro Tech) and human IL-2 (Pepro Tech) were added at a final concentration of 10 ng/ml and 50 ng/ml, respectively.
  • the cells were incubated in a 5% CO 2 incubator at 37° C. for 5 days.
  • the cells were peeled with a scraper, washed once with the medium, and suspended in 10% FBS/RPMI1640 medium at a density of 5 ⁇ 10 6 cells/ml to prepare a mouse marrow-derived effector cell suspension.
  • HepG2 Human hepatic cancer cells HepG2 (purchased from ATCC) were maintained in RPMI1640 medium (SIGMA) containing 10% FBS (Thermo Trace). The cells were peeled from the dish using Cell Dissociation Buffer (Invitrogen), and transferred to each well of a 96-well U-bottomed plate (Falcon) at a density of 1 ⁇ 10 4 cells/well, and incubated for 1 day. After the incubation, 5.55 MBq of Chromium-51 was added and the cells were further incubated in a 5% CO 2 incubator at 37° C. for 4 hours. The cells were washed once with the medium, and suspended in 50 ⁇ l of 10% FBS/RPMI1640 medium to prepare target cells.
  • SIGMA Cell Dissociation Buffer
  • Falcon 96-well U-bottomed plate
  • the experiment was carried out in triplicate, and the mean value of the ADCC activity (%) of the sample was calculated.
  • the Fc-modified humanized anti-glypican-3 antibody is useful in treating cancers, such as hepatic cancer.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cell Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Steroid Compounds (AREA)
US11/251,561 2005-10-14 2005-10-14 Anti-glypican-3 antibody Abandoned US20070087005A1 (en)

Priority Applications (16)

Application Number Priority Date Filing Date Title
US11/251,561 US20070087005A1 (en) 2005-10-14 2005-10-14 Anti-glypican-3 antibody
US12/089,957 US9102739B2 (en) 2005-10-14 2006-10-11 Anti-glypican-3 antibody
JP2008535637A JP5303274B2 (ja) 2005-10-14 2006-10-11 抗グリピカン３抗体
BRPI0617412A BRPI0617412B8 (pt) 2005-10-14 2006-10-11 anticorpo antiglipicano-3, agente anticâncer compreendendo o mesmo, bem como seu uso e seu processo de produção
AU2006304100A AU2006304100C1 (en) 2005-10-14 2006-10-11 Anti-glypican-3 antibody
PCT/US2006/039682 WO2007047291A2 (fr) 2005-10-14 2006-10-11 Anticorps anti-glypicane 3
CA2624894A CA2624894C (fr) 2005-10-14 2006-10-11 Anticorps anti-glypicane 3
CN2006800379295A CN101287492B (zh) 2005-10-14 2006-10-11 抗-磷脂酰肌醇蛋白聚糖-3抗体
ES06825738.5T ES2470374T3 (es) 2005-10-14 2006-10-11 Anticuerpo anti-glipicano 3
EP06825738.5A EP1933872B1 (fr) 2005-10-14 2006-10-11 Anticorps anti-glypicane 3
CN201210178007.3A CN102850455B (zh) 2005-10-14 2006-10-11 抗-磷脂酰肌醇蛋白聚糖-3抗体
KR1020087009364A KR101397858B1 (ko) 2005-10-14 2006-10-11 항-글리피칸-3 항체
IL190472A IL190472A (en) 2005-10-14 2008-03-27 Glyphican Antibody 3 Methods for their preparation and use
HK08113479.5A HK1120427A1 (en) 2005-10-14 2008-12-11 Anti-glypican-3 antibody
HK13103286.2A HK1176076A1 (en) 2005-10-14 2008-12-11 Anti-glypican-3 antibody --3
US14/505,932 US10118959B2 (en) 2005-10-14 2014-10-03 Anti-glypican-3 antibody

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US11/251,561 US20070087005A1 (en) 2005-10-14 2005-10-14 Anti-glypican-3 antibody

Related Child Applications (3)

Application Number Title Priority Date Filing Date
US12/089,957 Continuation US9102739B2 (en) 2005-10-14 2006-10-11 Anti-glypican-3 antibody
US12/089,957 Continuation-In-Part US9102739B2 (en) 2005-10-14 2006-10-11 Anti-glypican-3 antibody
US14/505,932 Continuation US10118959B2 (en) 2005-10-14 2014-10-03 Anti-glypican-3 antibody

Publications (1)

Publication Number Publication Date
US20070087005A1 true US20070087005A1 (en) 2007-04-19

Family

ID=37890328

Family Applications (3)

Application Number Title Priority Date Filing Date
US11/251,561 Abandoned US20070087005A1 (en) 2005-10-14 2005-10-14 Anti-glypican-3 antibody
US12/089,957 Active 2026-10-04 US9102739B2 (en) 2005-10-14 2006-10-11 Anti-glypican-3 antibody
US14/505,932 Active 2027-07-01 US10118959B2 (en) 2005-10-14 2014-10-03 Anti-glypican-3 antibody

Family Applications After (2)

Application Number Title Priority Date Filing Date
US12/089,957 Active 2026-10-04 US9102739B2 (en) 2005-10-14 2006-10-11 Anti-glypican-3 antibody
US14/505,932 Active 2027-07-01 US10118959B2 (en) 2005-10-14 2014-10-03 Anti-glypican-3 antibody

Country Status (12)

Country Link
US (3) US20070087005A1 (fr)
EP (1) EP1933872B1 (fr)
JP (1) JP5303274B2 (fr)
KR (1) KR101397858B1 (fr)
CN (2) CN102850455B (fr)
AU (1) AU2006304100C1 (fr)
BR (1) BRPI0617412B8 (fr)
CA (1) CA2624894C (fr)
ES (1) ES2470374T3 (fr)
HK (2) HK1120427A1 (fr)
IL (1) IL190472A (fr)
WO (1) WO2007047291A2 (fr)

Cited By (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040132101A1 (en) * 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
US20050215768A1 (en) * 2003-10-17 2005-09-29 Armour Kathryn L Polypeptides including modified constant regions
US20070135620A1 (en) * 2004-11-12 2007-06-14 Xencor, Inc. Fc variants with altered binding to FcRn
US20070160597A1 (en) * 2002-03-01 2007-07-12 Xencor, Inc. Optimized Fc variants and methods for their generation
US20070190599A1 (en) * 2004-07-09 2007-08-16 Kiyotaka Nakano Anti-glypican 3 antibody
US20070202098A1 (en) * 2002-03-01 2007-08-30 Xencor, Inc. Her2/neu OPTIMIZED Fc VARIANTS AND METHODS FOR THEIR GENERATION
US20070231329A1 (en) * 2003-03-03 2007-10-04 Xencor, Inc. Fc Variants Having Increased Affinity for FcyRIIb
US20070269444A1 (en) * 2004-08-24 2007-11-22 Chugai Seiyaku Kabushiki Kaisha Adjuvant Therapy with the Use of Anti-Glypican 3 Antibody
WO2007137170A2 (fr) * 2006-05-20 2007-11-29 Seattle Genetics, Inc. Conjugués médicamenteux d'anticorps anti-glypicane-3
US20080051563A1 (en) * 2003-03-03 2008-02-28 Xencor, Inc. Fc Variants with Increased Affinity for FcyRIIc
US20080124330A1 (en) * 2004-10-26 2008-05-29 Chugai Seiyaku Kabushiki Kaisha Anti-Glypican 3 Antibody Having Modified Sugar Chain
US20080267979A1 (en) * 2005-10-14 2008-10-30 Gregory Alan Lazar Anti-Glypican-3 Antibody
US20090041770A1 (en) * 2004-11-12 2009-02-12 Chamberlain Aaron Keith Fc VARIANTS WITH ALTERED BINDING TO FcRn
US20090053240A1 (en) * 2004-10-21 2009-02-26 Xencor, Inc. Novel Immunoglobulin Insertions, Deletions and Substitutions
WO2009009103A3 (fr) * 2007-07-10 2009-03-19 Medimmune Llc Cristaux et structure du variant d'igg fc humain
US20090163699A1 (en) * 2004-11-12 2009-06-25 Chamberlain Aaron Keith Fc VARIANTS WITH ALTERED BINDING TO FcRn
US20100239577A1 (en) * 2007-09-28 2010-09-23 Chugai Seiyaku Kabushiki Kaisha Anti-glypican-3 antibody having improved kinetics in plasma
US20100249382A1 (en) * 2005-10-03 2010-09-30 Xencor, Inc. MODIFIED Fc MOLECULES
EP2275135A1 (fr) * 2008-04-04 2011-01-19 Chugai Seiyaku Kabushiki Kaisha Thérapie pour cancer hépatique
US20110229903A1 (en) * 2008-10-23 2011-09-22 Ulrich Goepfert Determination of immunoglobulin encoding nucleic acid
US8546543B2 (en) 2004-11-12 2013-10-01 Xencor, Inc. Fc variants that extend antibody half-life
US9051373B2 (en) 2003-05-02 2015-06-09 Xencor, Inc. Optimized Fc variants
US9200079B2 (en) 2004-11-12 2015-12-01 Xencor, Inc. Fc variants with altered binding to FcRn
WO2015179658A3 (fr) * 2014-05-22 2016-01-21 Genentech, Inc. Immunoconjugués et anticorps anti-gpc3
US9475881B2 (en) 2010-01-19 2016-10-25 Xencor, Inc. Antibody variants with enhanced complement activity
US9714282B2 (en) 2003-09-26 2017-07-25 Xencor, Inc. Optimized Fc variants and methods for their generation
US9926377B2 (en) 2014-05-22 2018-03-27 Genentech, Inc. Anti-GPC3 antibodies and immunoconjugates
US9975966B2 (en) 2014-09-26 2018-05-22 Chugai Seiyaku Kabushiki Kaisha Cytotoxicity-inducing theraputic agent
US10736976B2 (en) 2016-12-01 2020-08-11 Regeneron Pharmaceuticals, Inc. Radiolabeled anti-PD-L1 antibodies for immuno-PET imaging
US10782300B2 (en) 2012-12-21 2020-09-22 Chugai Seiyaku Kabushiki Kaisha GPC3-targeting drug which is administered to patient responsive to GPC3-targeting drug therapy
US10918698B2 (en) * 2014-03-29 2021-02-16 Intas Pharmaceuticals Ltd. Lyophilized pharmaceutical composition of Fc-peptide fusion protein
US11376326B2 (en) 2015-07-01 2022-07-05 Chugai Seiyaku Kabushiki Kaisha GPC3-targeting therapeutic agent which is administered to patient for whom the GPC3-targeting therapeutic agent is effective
US11401348B2 (en) 2009-09-02 2022-08-02 Xencor, Inc. Heterodimeric Fc variants
US11760807B2 (en) 2014-05-08 2023-09-19 Chugai Seiyaku Kabushiki Kaisha GPC3-targeting drug which is administered to patient responsive to GPC3-targeting drug therapy
US11767362B1 (en) 2016-03-15 2023-09-26 Chugai Seiyaku Kabushiki Kaisha Methods of treating cancers using PD-1 axis binding antagonists and anti-GPC3 antibodies
US11820830B2 (en) 2004-07-20 2023-11-21 Xencor, Inc. Optimized Fc variants
US11932685B2 (en) 2007-10-31 2024-03-19 Xencor, Inc. Fc variants with altered binding to FcRn

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004022597A1 (fr) * 2002-09-04 2004-03-18 Chugai Seiyaku Kabushiki Kaisha Anticorps d'un peptide n-terminal du gpc3 solubilise dans le sang
US20110123440A1 (en) * 2005-03-29 2011-05-26 Genevieve Hansen Altered Antibody FC Regions and Uses Thereof
KR101105428B1 (ko) * 2009-02-12 2012-01-17 경북대학교 산학협력단 글리피칸-3 단백질과 특이적으로 결합하는 펩타이드
CA2817779C (fr) 2010-11-15 2019-02-19 Pieris Ag Muteines de lipocaline humaine 2 ayant de l'affinite pour le glypicane-3 (gpc3)
EP3511336B1 (fr) * 2011-06-28 2023-06-21 Leukocare Ag Procédé pour empêcher le dépliage d'un (poly)peptide et/ou induire le (re-)pliage d'un (poly)peptide
CN102898524A (zh) * 2011-07-25 2013-01-30 中国医学科学院基础医学研究所 抗人肿瘤坏死因子相关凋亡诱导配体受体dr5的人-鼠嵌合抗体及其制法与用途
CN104520331B (zh) 2012-06-01 2018-09-07 美国政府(由卫生和人类服务部的部长所代表) 磷脂酰肌醇蛋白聚糖3的高亲和力单克隆抗体及其用途
EP4310191A3 (fr) * 2012-06-14 2024-05-15 Chugai Seiyaku Kabushiki Kaisha Molécule de liaison à l'antigène contenant une région fc modifiée
EP4119947A1 (fr) 2012-12-21 2023-01-18 Chugai Seiyaku Kabushiki Kaisha Médicament de ciblage gpc3 administré à un patient en réponse à une thérapie médicamenteuse de ciblage gpc3
ES2876009T3 (es) 2012-12-27 2021-11-11 Chugai Pharmaceutical Co Ltd Polipéptido heterodimerizado
CA2929044A1 (fr) 2013-11-11 2015-05-14 Chugai Seiyaku Kabushiki Kaisha Molecule se liant a l'antigene contenant une region variable d'anticorps modifiee
TWI740809B (zh) 2014-11-11 2021-10-01 日商中外製藥股份有限公司 包含經改變之抗體可變區之抗原結合分子的資料庫
CN104829704B (zh) * 2014-12-15 2016-08-17 河北省科学院生物研究所 一种磷脂酰肌醇蛋白聚糖gpc3蛋白片段及其应用和制备的杂交瘤细胞株
AU2015376851B2 (en) * 2015-01-16 2020-07-09 Minomic International Ltd. Glypican epitopes and uses thereof
CN104610441B (zh) * 2015-03-04 2018-02-13 首都医科大学 用于制备磷脂酰肌醇蛋白聚糖‑3(gpc3)单抗的人工半抗原、制备方法及获得的单克隆抗体
CN114456252A (zh) 2015-05-18 2022-05-10 皮里斯制药有限公司 对磷脂酰肌醇聚糖-3（gpc3）具有亲和力的人脂质运载蛋白2的突变蛋白
ES2938525T3 (es) 2015-05-18 2023-04-12 Pieris Pharmaceuticals Gmbh Polipéptido de fusión anticanceroso
GB2541166A (en) 2015-07-24 2017-02-15 Midatech Ltd Nanoparticle-based liver-targeting therapy and imaging
DK3333192T3 (da) * 2015-08-03 2021-05-31 Cafa Therapeutics Ltd Antistof imod glypican-3 og anvendelse deraf
AU2017301826A1 (en) 2016-07-26 2019-03-14 Tessa Therapeutics Ltd. Chimeric antigen receptor
WO2018038046A1 (fr) 2016-08-22 2018-03-01 中外製薬株式会社 Animal non humain à gène modifié exprimant le polypeptide (gpc3) humain
WO2018208628A1 (fr) 2017-05-06 2018-11-15 Memphis Meats, Inc. Compositions et procédés permettant d'augmenter la densité de culture d'une biomasse cellulaire dans une infrastructure de culture
EA201992755A1 (ru) 2017-05-19 2020-04-22 Уси Байолоджикс (Шанхай) Ко. Лтд. Новые моноклональные антитела к белку 4, ассоциированному с цитотоксическими т-лимфоцитами, (ctla-4)
EP3638777A4 (fr) 2017-07-13 2021-05-12 Memphis Meats, Inc. Compositions et procédés pour augmenter l'efficacité de cultures cellulaires utilisées pour la production d'aliments
US20200216542A1 (en) 2017-09-20 2020-07-09 Chugai Seiyaku Kabushiki Kaisha Dosage regimen for combination therapy using pd-1 axis binding antagonists and gpc3 targeting agent
WO2019111871A1 (fr) 2017-12-05 2019-06-13 Chugai Seiyaku Kabushiki Kaisha Molécule de liaison à l'antigène comprenant une région variable d'anticorps modifiée se liant à cd3 et cd137
AU2019333315B2 (en) * 2018-08-30 2022-09-29 Tenaya Therapeutics, Inc. Cardiac cell reprogramming with myocardin and ASCL1
KR20210087458A (ko) 2018-10-01 2021-07-12 아디셋 바이오, 인크. 고형 종양 치료를 위한 조작된 및 비-조작된 γδ-T 세포에 관한 조성물 및 방법
EP3902833A2 (fr) * 2018-12-26 2021-11-03 City of Hope Protéines de liaison anti-ctla4 masquées activables
CN110872351B (zh) * 2019-09-06 2022-06-17 广西科技大学 一种特异性结合gpc3蛋白的纳米抗体gn1及其制备方法和应用
CN111320694B (zh) * 2020-02-15 2022-07-22 广西科技大学 一种由重链抗体的可变区组成的纳米抗体gn2及其制备方法和应用
KR20230035138A (ko) 2020-03-31 2023-03-10 추가이 세이야쿠 가부시키가이샤 Dll3 표적 다중 특이성 항원 결합 분자 및 그의 사용
CN113354737B (zh) * 2021-07-20 2022-11-18 广州爱思迈生物医药科技有限公司 一种磷脂酰肌醇蛋白聚糖3抗体及其应用
WO2023092099A1 (fr) * 2021-11-19 2023-05-25 Ardeagen Corporation Agents de liaison de gpc3, leurs conjugués et leurs procédés d'utilisation

Citations (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5530101A (en) * 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US6165745A (en) * 1992-04-24 2000-12-26 Board Of Regents, The University Of Texas System Recombinant production of immunoglobulin-like domains in prokaryotic cells
US6210670B1 (en) * 1994-06-14 2001-04-03 Protein Design Labs, Inc. Cross-reacting monoclonal antibodies specific for E-selectin and P-selectin
US20030103970A1 (en) * 1997-10-03 2003-06-05 Masayuki Tsuchiya Natural human antibody
US20030175884A1 (en) * 2001-08-03 2003-09-18 Pablo Umana Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US20040024320A1 (en) * 2001-11-14 2004-02-05 Hirokazu Karasawa Ultrasonograph, ultrasonic transducer, examining instrument, and ultrasonographing device
US6737056B1 (en) * 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
US20040132101A1 (en) * 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
US20040236080A1 (en) * 2001-06-22 2004-11-25 Hiroyuki Aburatani Cell proliferation inhibitors containing anti-glypican 3 antibody
US20050171339A1 (en) * 2001-12-28 2005-08-04 Izumi Sugo Method of stabilizing protein
US20050233392A1 (en) * 2002-05-23 2005-10-20 Jorge Filmus Diagnosis of hepatocellular carcinoma
US20060024298A1 (en) * 2002-09-27 2006-02-02 Xencor, Inc. Optimized Fc variants
US20060040325A1 (en) * 2004-08-16 2006-02-23 Medimmune, Inc. Integrin antagonists with enhanced antibody dependent cell-mediated cytoxicity activity
US20060167232A1 (en) * 2002-09-04 2006-07-27 Chugai Seiyaku Kabushiki Kaisha Antibody against n-terminal peptide or c-terminal peptide of gpc3 solubilized in blood
US7297775B2 (en) * 1998-04-02 2007-11-20 Genentech, Inc. Polypeptide variants
US7317091B2 (en) * 2002-03-01 2008-01-08 Xencor, Inc. Optimized Fc variants
US20080051563A1 (en) * 2003-03-03 2008-02-28 Xencor, Inc. Fc Variants with Increased Affinity for FcyRIIc
US7361336B1 (en) * 1997-09-18 2008-04-22 Ivan Bergstein Methods of cancer therapy targeted against a cancer stem line
US20080166756A1 (en) * 2004-12-22 2008-07-10 Masayuki Tsuchiya Method of Producing an Antibody Using a Cell in Which the Function of Fucose Transporter Is Inhibited
US7662925B2 (en) * 2002-03-01 2010-02-16 Xencor, Inc. Optimized Fc variants and methods for their generation
US20100248359A1 (en) * 2004-07-09 2010-09-30 Chugai Seiyaku Kabushiki Kaisha Anti-Glypican 3 Antibody
US7867734B2 (en) * 2004-10-26 2011-01-11 Chugai Seiyaku Kabushiki Kaisha Anti-glypican 3 antibody having modified sugar chain
US7871613B2 (en) * 2004-08-24 2011-01-18 Chugai Seiyaku Kabushiki Kaisha Adjuvant therapy with the use of anti-glypican 3 antibody
US20110091907A1 (en) * 2008-03-17 2011-04-21 University Of Miyazaki Method for detection of liver cancer cell using anti-glypican-3 antibody
US20110104157A1 (en) * 2008-04-04 2011-05-05 Chugai Seiyaku Kabushiki Kaisha Liver cancer drug

Family Cites Families (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5322678A (en) 1988-02-17 1994-06-21 Neorx Corporation Alteration of pharmacokinetics of proteins by charge modification
JPH0242355A (ja) 1988-08-02 1990-02-13 Hitachi Constr Mach Co Ltd 超音波検査装置
JPH04336051A (ja) 1991-05-10 1992-11-24 Toshiba Corp 超音波診断装置
AU3272695A (en) 1994-08-12 1996-03-07 Immunomedics Inc. Immunoconjugates and humanized antibodies specific for b-cell lymphoma and leukemia cells
WO1998023289A1 (fr) 1996-11-27 1998-06-04 The General Hospital Corporation Modulation de la fixation de l'igg au fcrn
US6617156B1 (en) 1997-08-15 2003-09-09 Lynn A. Doucette-Stamm Nucleic acid and amino acid sequences relating to Enterococcus faecalis for diagnostics and therapeutics
JPH11118775A (ja) 1997-10-09 1999-04-30 Canon Inc 超音波検査装置
WO1999054342A1 (fr) 1998-04-20 1999-10-28 Pablo Umana Modification par glycosylation d'anticorps aux fins d'amelioration de la cytotoxicite cellulaire dependant des anticorps
MXPA01008110A (es) 1999-02-12 2002-10-23 Scripps Research Inst Metodos para el tratamiento de tumores y metastasis utilizando una combinacion de terapias anti-angiogenicas e inmunoterapia.
JP4368530B2 (ja) 1999-04-09 2009-11-18 協和発酵キリン株式会社 免疫機能分子の活性を調節する方法
JP3606132B2 (ja) 1999-10-14 2005-01-05 Ｊｆｅエンジニアリング株式会社 超音波探傷方法およびその装置
ES2527754T3 (es) 2000-04-25 2015-01-29 Icos Corporation Inhibidores de la isoforma delta de la fosfatidilinositol 3-quinasa humana
NZ505538A (en) 2000-07-03 2004-12-24 Malaghan Inst Of Medical Res A vaccine comprising immunogenic acyl glyceryl phosphatidylinositol manno-oligosaccharide (PIM); and the use of PIM for inducing an immune response in a patient effective in the prevention or treatment of Th2-mediated diseases or disorders such as asthma
GB0017635D0 (en) 2000-07-18 2000-09-06 Pharmacia & Upjohn Spa Antitumor combined therapy
JP2002048867A (ja) 2000-08-07 2002-02-15 Mitsubishi Heavy Ind Ltd 音響探査装置
US6825273B2 (en) 2000-09-12 2004-11-30 Union Carbide Chemicals & Plastics Technology Corporation Polymer composites containing alkylene oxide copolymers
CN103333860B (zh) 2000-10-06 2015-07-08 协和发酵麒麟株式会社 产生抗体组合物的细胞
US6436411B1 (en) 2000-10-23 2002-08-20 The Center For The Improvement Of Human Functioning, Int'l., Inc. Cancer treatment method
WO2002040545A2 (fr) 2000-11-17 2002-05-23 The Government Of The United States, As Represented By The Secretary Of The Department Of Health And Human Services Reduction de la toxicite animale non specifique des immunotoxines par mutation des regions d'infrastructure de fv pour reduire le point isoelectrique
CA2442801A1 (fr) 2001-04-02 2002-10-10 Idec Pharmaceutical Corporation Anticorps recombinants co-exprimes avec gntiii
JP4087098B2 (ja) 2001-11-14 2008-05-14 株式会社東芝 超音波検査装置
JP3961359B2 (ja) 2002-07-18 2007-08-22 株式会社東芝 超音波画像化装置
WO2003074679A2 (fr) 2002-03-01 2003-09-12 Xencor Optimisation d'anticorps
CA2481658A1 (fr) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Procede d'amelioration de l'activite d'une composition d'anticorps de liaison avec le recepteur fcy iiia
JP4406607B2 (ja) 2002-08-26 2010-02-03 オンコセラピー・サイエンス株式会社 ペプチド及びこれを含む医薬
WO2004023145A1 (fr) 2002-09-04 2004-03-18 Perseus Proteomics Inc. Procede de detection du cancer par detection du gpc3
AU2002328429A1 (en) 2002-09-04 2004-03-29 Chugai Seiyaku Kabushiki Kaisha CONSTRUCTION OF ANTIBODY USING MRL/lpr MOUSE
SI2345671T1 (sl) 2002-09-27 2016-03-31 Xencor Inc. Optimizirane Fc-variante in postopki za njihovo izdelavo
JPWO2005023301A1 (ja) 2003-09-04 2006-11-02 中外製薬株式会社 胆管癌治療剤および検出薬
US20050161541A1 (en) * 2004-01-28 2005-07-28 Emily Lo Fragmenting devices for shredding paper and breaking compact discs
ITBO20040008U1 (it) 2004-02-03 2004-05-03 Tonazzi S R L Macchina per il riempimento e la chiusura di tubetti
JP4658926B2 (ja) 2004-04-28 2011-03-23 株式会社ペルセウスプロテオミクス 肝癌治療後の再発予測判定薬
CA2569277A1 (fr) 2004-06-04 2005-12-15 Pfizer Products Inc. Methode de traitement de croissances cellulaires anormales
PE20061401A1 (es) 2004-12-15 2006-12-23 Neuralab Ltd ANTICUERPOS Aß PARA MEJORAR LA COGNICION
US8309690B2 (en) 2005-07-01 2012-11-13 Medimmune, Llc Integrated approach for generating multidomain protein therapeutics
JP2007093274A (ja) 2005-09-27 2007-04-12 Perseus Proteomics Inc 癌の診断方法および治療薬
US20070087005A1 (en) * 2005-10-14 2007-04-19 Lazar Gregory A Anti-glypican-3 antibody
CA2627873A1 (fr) 2005-10-31 2007-05-10 Scott Wilhelm Traitement du cancer au moyen de sorafenib
EP1973576B1 (fr) 2005-11-28 2019-05-15 Genmab A/S Anticorps monovalents recombines et leurs procedes de production
TW200800181A (en) 2006-02-09 2008-01-01 Sankyo Co Pharmaceutical composition for anticancer
WO2007099988A1 (fr) 2006-02-28 2007-09-07 Kyowa Hakko Kogyo Co., Ltd. mutant de α-1,6-FUCOSYLTRANSFERASE et son utilisation
WO2007137170A2 (fr) 2006-05-20 2007-11-29 Seattle Genetics, Inc. Conjugués médicamenteux d'anticorps anti-glypicane-3
EP2062047B1 (fr) 2006-09-13 2011-03-09 Glycode Methode d'investigation de la reponse a un traitement par un anticorps monoclonal
RU2510400C9 (ru) 2007-09-26 2014-07-20 Чугаи Сейяку Кабусики Кайся Способ модификации изоэлектрической точки антитела с помощью аминокислотных замен в cdr
RU2010116756A (ru) 2007-09-28 2011-11-10 Чугаи Сейяку Кабусики Кайся (Jp) Антитело против глипикана-3 с улучшенными кинетическими показателями в плазме
CN101377506A (zh) 2008-04-16 2009-03-04 北京科美东雅生物技术有限公司 磷脂酰肌醇蛋白聚糖-3化学发光免疫分析测定试剂盒及其制备方法
CA2725666A1 (fr) 2008-06-03 2009-12-10 Abbott Laboratories Immunoglobulines a double domaine variable et leurs utilisations
CN102276721B (zh) 2010-06-12 2013-12-25 上海市肿瘤研究所 一种用于肝癌血清学诊断的单克隆抗体及其用途
CN103596985B (zh) 2011-04-19 2016-06-08 美国政府(由卫生和人类服务部的部长所代表) 对磷脂酰肌醇蛋白聚糖3特异的人单克隆抗体及其用途
JP6226752B2 (ja) 2012-02-09 2017-11-08 中外製薬株式会社 抗体のＦｃ領域改変体
RU2014138586A (ru) 2012-03-02 2016-04-20 Рош Гликарт Аг Прогностический биомаркер для лечения рака антителами с повышенной антителозависимой клеточной цитотоксичностью
TWI693073B (zh) 2012-12-21 2020-05-11 日商中外製藥股份有限公司 對ｇｐｃ３標的治療劑療法為有效之患者投與的ｇｐｃ３標的治療劑

Patent Citations (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5530101A (en) * 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US6165745A (en) * 1992-04-24 2000-12-26 Board Of Regents, The University Of Texas System Recombinant production of immunoglobulin-like domains in prokaryotic cells
US6210670B1 (en) * 1994-06-14 2001-04-03 Protein Design Labs, Inc. Cross-reacting monoclonal antibodies specific for E-selectin and P-selectin
US7427400B2 (en) * 1997-09-18 2008-09-23 Ivan Bergstein Methods of cancer diagnosis and therapy targeted against a cancer stem line
US7361336B1 (en) * 1997-09-18 2008-04-22 Ivan Bergstein Methods of cancer therapy targeted against a cancer stem line
US20030103970A1 (en) * 1997-10-03 2003-06-05 Masayuki Tsuchiya Natural human antibody
US7297775B2 (en) * 1998-04-02 2007-11-20 Genentech, Inc. Polypeptide variants
US6737056B1 (en) * 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
US20040236080A1 (en) * 2001-06-22 2004-11-25 Hiroyuki Aburatani Cell proliferation inhibitors containing anti-glypican 3 antibody
US20070172488A1 (en) * 2001-06-22 2007-07-26 Chugai Seiyaku Kabushiki Kaisha Cell growth inhibitors containing anti-glypican 3 antibody
US20030175884A1 (en) * 2001-08-03 2003-09-18 Pablo Umana Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US20040024320A1 (en) * 2001-11-14 2004-02-05 Hirokazu Karasawa Ultrasonograph, ultrasonic transducer, examining instrument, and ultrasonographing device
US20050171339A1 (en) * 2001-12-28 2005-08-04 Izumi Sugo Method of stabilizing protein
US20060287508A1 (en) * 2001-12-28 2006-12-21 Izumi Sugo Methods for stabilizing proteins
US7317091B2 (en) * 2002-03-01 2008-01-08 Xencor, Inc. Optimized Fc variants
US20080181890A1 (en) * 2002-03-01 2008-07-31 Xencor, Inc. Optimized Fc Variants and Methods for Their Generation
US7662925B2 (en) * 2002-03-01 2010-02-16 Xencor, Inc. Optimized Fc variants and methods for their generation
US20050233392A1 (en) * 2002-05-23 2005-10-20 Jorge Filmus Diagnosis of hepatocellular carcinoma
US20060167232A1 (en) * 2002-09-04 2006-07-27 Chugai Seiyaku Kabushiki Kaisha Antibody against n-terminal peptide or c-terminal peptide of gpc3 solubilized in blood
US20100183595A1 (en) * 2002-09-04 2010-07-22 Chugai Seiyaku Kabushiki Kaisha Antibody against secreted N-terminal peptide of GPC3 present in blood or C-terminal peptide of GPC3
US20090060907A1 (en) * 2002-09-04 2009-03-05 Chugai Seiyaku Kabushiki Kaisha Antibody against secreted N-terminal peptide of GPC3 present in blood or C-terminal peptide of GPC3
US20060188510A1 (en) * 2002-09-04 2006-08-24 Chugai Seiyaku Kabushiki Kaisha Antibody against secreted N-terminal peptide of GPC3 present in blood or C-terminal peptide of GPC3
US20040132101A1 (en) * 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
US8039592B2 (en) * 2002-09-27 2011-10-18 Xencor, Inc. Optimized Fc variants and methods for their generation
US20060024298A1 (en) * 2002-09-27 2006-02-02 Xencor, Inc. Optimized Fc variants
US20080161541A1 (en) * 2003-03-03 2008-07-03 Xencor, Inc. Fc Variants with Increased Affinity for FcyRIIc
US20080154025A1 (en) * 2003-03-03 2008-06-26 Xencor, Inc. Fc Variants with Increased Affinity for FcyRIIc
US20080051563A1 (en) * 2003-03-03 2008-02-28 Xencor, Inc. Fc Variants with Increased Affinity for FcyRIIc
US20100248359A1 (en) * 2004-07-09 2010-09-30 Chugai Seiyaku Kabushiki Kaisha Anti-Glypican 3 Antibody
US7919086B2 (en) * 2004-07-09 2011-04-05 Chugai Seiyaku Kabushiki Kaisha Anti-glypican 3 antibody
US20060040325A1 (en) * 2004-08-16 2006-02-23 Medimmune, Inc. Integrin antagonists with enhanced antibody dependent cell-mediated cytoxicity activity
US7871613B2 (en) * 2004-08-24 2011-01-18 Chugai Seiyaku Kabushiki Kaisha Adjuvant therapy with the use of anti-glypican 3 antibody
US7867734B2 (en) * 2004-10-26 2011-01-11 Chugai Seiyaku Kabushiki Kaisha Anti-glypican 3 antibody having modified sugar chain
US20110033452A1 (en) * 2004-10-26 2011-02-10 Chugai Seiyaku Kabushiki Kaisha Anti-Glypican 3 Antibody Having Modified Sugar Chain
US20080166756A1 (en) * 2004-12-22 2008-07-10 Masayuki Tsuchiya Method of Producing an Antibody Using a Cell in Which the Function of Fucose Transporter Is Inhibited
US20110091907A1 (en) * 2008-03-17 2011-04-21 University Of Miyazaki Method for detection of liver cancer cell using anti-glypican-3 antibody
US20110104157A1 (en) * 2008-04-04 2011-05-05 Chugai Seiyaku Kabushiki Kaisha Liver cancer drug

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DiPiro et al. Concepts in Clinical Pharmacokinetics. 5th Edition, American Society of Health-System Pharmacists 2010. Lesson 2, pages 19-28. *
The Bjorkman declaration, 01/18/2011, pages 1-14. *
Wang et al. Clinical Pharmacology& Therapeutics 2008, November 84;5:548-558. *

Cited By (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070202098A1 (en) * 2002-03-01 2007-08-30 Xencor, Inc. Her2/neu OPTIMIZED Fc VARIANTS AND METHODS FOR THEIR GENERATION
US20070224189A1 (en) * 2002-03-01 2007-09-27 Xencor, Inc. CD20 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
US20070160597A1 (en) * 2002-03-01 2007-07-12 Xencor, Inc. Optimized Fc variants and methods for their generation
US20070219133A1 (en) * 2002-03-01 2007-09-20 Xencor, Inc. CD52 OPTIMIZED Fc VARIANTS AND METHODS FOR THEIR GENERATION
US8809503B2 (en) 2002-09-27 2014-08-19 Xencor, Inc. Optimized Fc variants and methods for their generation
US8039592B2 (en) 2002-09-27 2011-10-18 Xencor, Inc. Optimized Fc variants and methods for their generation
US8093359B2 (en) 2002-09-27 2012-01-10 Xencor, Inc. Optimized Fc variants and methods for their generation
US20090068177A1 (en) * 2002-09-27 2009-03-12 Xencor, Inc. Optimized Fc variants and methods for their generation
US8858937B2 (en) 2002-09-27 2014-10-14 Xencor, Inc. Optimized Fc variants and methods for their generation
US9193798B2 (en) 2002-09-27 2015-11-24 Xencor, Inc. Optimized Fc variants and methods for their generation
US9353187B2 (en) 2002-09-27 2016-05-31 Xencor, Inc. Optimized FC variants and methods for their generation
US20040132101A1 (en) * 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
US20090092599A1 (en) * 2002-09-27 2009-04-09 Xencor, Inc. Optimized Fc variants and methods for their generation
US20090081208A1 (en) * 2002-09-27 2009-03-26 Xencor, Inc. Optimized Fc variants and methods for their generation
US10184000B2 (en) 2002-09-27 2019-01-22 Xencor, Inc. Optimized Fc variants and methods for their generation
US8383109B2 (en) 2002-09-27 2013-02-26 Xencor, Inc. Optimized Fc variants and methods for their generation
US10183999B2 (en) 2002-09-27 2019-01-22 Xencor, Inc. Optimized Fc variants and methods for their generation
US10113001B2 (en) 2003-03-03 2018-10-30 Xencor, Inc. Fc variants with increased affinity for FcyRIIc
US8937158B2 (en) 2003-03-03 2015-01-20 Xencor, Inc. Fc variants with increased affinity for FcγRIIc
US20090010920A1 (en) * 2003-03-03 2009-01-08 Xencor, Inc. Fc Variants Having Decreased Affinity for FcyRIIb
US20080161541A1 (en) * 2003-03-03 2008-07-03 Xencor, Inc. Fc Variants with Increased Affinity for FcyRIIc
US20080154025A1 (en) * 2003-03-03 2008-06-26 Xencor, Inc. Fc Variants with Increased Affinity for FcyRIIc
US8388955B2 (en) 2003-03-03 2013-03-05 Xencor, Inc. Fc variants
US20070231329A1 (en) * 2003-03-03 2007-10-04 Xencor, Inc. Fc Variants Having Increased Affinity for FcyRIIb
US9663582B2 (en) 2003-03-03 2017-05-30 Xencor, Inc. Optimized Fc variants
US9657106B2 (en) 2003-03-03 2017-05-23 Xencor, Inc. Optimized Fc variants
US20080051563A1 (en) * 2003-03-03 2008-02-28 Xencor, Inc. Fc Variants with Increased Affinity for FcyRIIc
US10584176B2 (en) 2003-03-03 2020-03-10 Xencor, Inc. Fc variants with increased affinity for FcγRIIc
US9051373B2 (en) 2003-05-02 2015-06-09 Xencor, Inc. Optimized Fc variants
US9714282B2 (en) 2003-09-26 2017-07-25 Xencor, Inc. Optimized Fc variants and methods for their generation
US20050215768A1 (en) * 2003-10-17 2005-09-29 Armour Kathryn L Polypeptides including modified constant regions
US20100248359A1 (en) * 2004-07-09 2010-09-30 Chugai Seiyaku Kabushiki Kaisha Anti-Glypican 3 Antibody
US7919086B2 (en) 2004-07-09 2011-04-05 Chugai Seiyaku Kabushiki Kaisha Anti-glypican 3 antibody
US20070190599A1 (en) * 2004-07-09 2007-08-16 Kiyotaka Nakano Anti-glypican 3 antibody
US11820830B2 (en) 2004-07-20 2023-11-21 Xencor, Inc. Optimized Fc variants
US7871613B2 (en) 2004-08-24 2011-01-18 Chugai Seiyaku Kabushiki Kaisha Adjuvant therapy with the use of anti-glypican 3 antibody
US20070269444A1 (en) * 2004-08-24 2007-11-22 Chugai Seiyaku Kabushiki Kaisha Adjuvant Therapy with the Use of Anti-Glypican 3 Antibody
US20090053240A1 (en) * 2004-10-21 2009-02-26 Xencor, Inc. Novel Immunoglobulin Insertions, Deletions and Substitutions
US8101720B2 (en) 2004-10-21 2012-01-24 Xencor, Inc. Immunoglobulin insertions, deletions and substitutions
US7867734B2 (en) 2004-10-26 2011-01-11 Chugai Seiyaku Kabushiki Kaisha Anti-glypican 3 antibody having modified sugar chain
US20080124330A1 (en) * 2004-10-26 2008-05-29 Chugai Seiyaku Kabushiki Kaisha Anti-Glypican 3 Antibody Having Modified Sugar Chain
US20110033452A1 (en) * 2004-10-26 2011-02-10 Chugai Seiyaku Kabushiki Kaisha Anti-Glypican 3 Antibody Having Modified Sugar Chain
US20090163699A1 (en) * 2004-11-12 2009-06-25 Chamberlain Aaron Keith Fc VARIANTS WITH ALTERED BINDING TO FcRn
US20100204454A1 (en) * 2004-11-12 2010-08-12 Xencor, Inc. Fc Variants with altered binding to FcRn
US8338574B2 (en) 2004-11-12 2012-12-25 Xencor, Inc. FC variants with altered binding to FCRN
US8367805B2 (en) 2004-11-12 2013-02-05 Xencor, Inc. Fc variants with altered binding to FcRn
US8318907B2 (en) 2004-11-12 2012-11-27 Xencor, Inc. Fc variants with altered binding to FcRn
US12215165B2 (en) 2004-11-12 2025-02-04 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
US11198739B2 (en) 2004-11-12 2021-12-14 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
US8802820B2 (en) 2004-11-12 2014-08-12 Xencor, Inc. Fc variants with altered binding to FcRn
US10336818B2 (en) 2004-11-12 2019-07-02 Xencor, Inc. Fc variants with altered binding to FcRn
US8852586B2 (en) 2004-11-12 2014-10-07 Xencor, Inc. Fc variants with altered binding to FcRn
US20090041770A1 (en) * 2004-11-12 2009-02-12 Chamberlain Aaron Keith Fc VARIANTS WITH ALTERED BINDING TO FcRn
US8883973B2 (en) 2004-11-12 2014-11-11 Xencor, Inc. Fc variants with altered binding to FcRn
US9803023B2 (en) 2004-11-12 2017-10-31 Xencor, Inc. Fc variants with altered binding to FcRn
US8324351B2 (en) 2004-11-12 2012-12-04 Xencor, Inc. Fc variants with altered binding to FcRn
US20100234573A1 (en) * 2004-11-12 2010-09-16 Xencor, Inc. Fc Variants with altered binding to FcRn
US20100234575A1 (en) * 2004-11-12 2010-09-16 Xencor, Inc. Fc variants with altered binding to fcrn
US9200079B2 (en) 2004-11-12 2015-12-01 Xencor, Inc. Fc variants with altered binding to FcRn
US20100234572A1 (en) * 2004-11-12 2010-09-16 Xencor, Inc. Fc Variants with altered binding to FcRn
US9040041B2 (en) 2005-10-03 2015-05-26 Xencor, Inc. Modified FC molecules
US20100249382A1 (en) * 2005-10-03 2010-09-30 Xencor, Inc. MODIFIED Fc MOLECULES
US10118959B2 (en) 2005-10-14 2018-11-06 Chugai Seiyaku Kabushiki Kaisha Anti-glypican-3 antibody
US9102739B2 (en) 2005-10-14 2015-08-11 Chugai Seiyaku Kabushiki Kaisha Anti-glypican-3 antibody
US20080267979A1 (en) * 2005-10-14 2008-10-30 Gregory Alan Lazar Anti-Glypican-3 Antibody
WO2007137170A3 (fr) * 2006-05-20 2009-05-14 Seattle Genetics Inc Conjugués médicamenteux d'anticorps anti-glypicane-3
WO2007137170A2 (fr) * 2006-05-20 2007-11-29 Seattle Genetics, Inc. Conjugués médicamenteux d'anticorps anti-glypicane-3
WO2009009103A3 (fr) * 2007-07-10 2009-03-19 Medimmune Llc Cristaux et structure du variant d'igg fc humain
US20100239577A1 (en) * 2007-09-28 2010-09-23 Chugai Seiyaku Kabushiki Kaisha Anti-glypican-3 antibody having improved kinetics in plasma
US8497355B2 (en) 2007-09-28 2013-07-30 Chugai Seiyaku Kabushiki Kaisha Anti-glypican-3 antibody having improved kinetics in plasma
US11932685B2 (en) 2007-10-31 2024-03-19 Xencor, Inc. Fc variants with altered binding to FcRn
US20110104157A1 (en) * 2008-04-04 2011-05-05 Chugai Seiyaku Kabushiki Kaisha Liver cancer drug
EP2275135A4 (fr) * 2008-04-04 2013-03-06 Chugai Pharmaceutical Co Ltd Thérapie pour cancer hépatique
EP2275135A1 (fr) * 2008-04-04 2011-01-19 Chugai Seiyaku Kabushiki Kaisha Thérapie pour cancer hépatique
TWI468175B (zh) * 2008-04-04 2015-01-11 Chugai Pharmaceutical Co Ltd Liver cancer treatment
US20110229903A1 (en) * 2008-10-23 2011-09-22 Ulrich Goepfert Determination of immunoglobulin encoding nucleic acid
US11401348B2 (en) 2009-09-02 2022-08-02 Xencor, Inc. Heterodimeric Fc variants
US9475881B2 (en) 2010-01-19 2016-10-25 Xencor, Inc. Antibody variants with enhanced complement activity
US10782300B2 (en) 2012-12-21 2020-09-22 Chugai Seiyaku Kabushiki Kaisha GPC3-targeting drug which is administered to patient responsive to GPC3-targeting drug therapy
US10918698B2 (en) * 2014-03-29 2021-02-16 Intas Pharmaceuticals Ltd. Lyophilized pharmaceutical composition of Fc-peptide fusion protein
US11760807B2 (en) 2014-05-08 2023-09-19 Chugai Seiyaku Kabushiki Kaisha GPC3-targeting drug which is administered to patient responsive to GPC3-targeting drug therapy
WO2015179658A3 (fr) * 2014-05-22 2016-01-21 Genentech, Inc. Immunoconjugués et anticorps anti-gpc3
US9926377B2 (en) 2014-05-22 2018-03-27 Genentech, Inc. Anti-GPC3 antibodies and immunoconjugates
US11001643B2 (en) 2014-09-26 2021-05-11 Chugai Seiyaku Kabushiki Kaisha Cytotoxicity-inducing therapeutic agent
US9975966B2 (en) 2014-09-26 2018-05-22 Chugai Seiyaku Kabushiki Kaisha Cytotoxicity-inducing theraputic agent
US11376326B2 (en) 2015-07-01 2022-07-05 Chugai Seiyaku Kabushiki Kaisha GPC3-targeting therapeutic agent which is administered to patient for whom the GPC3-targeting therapeutic agent is effective
US11767362B1 (en) 2016-03-15 2023-09-26 Chugai Seiyaku Kabushiki Kaisha Methods of treating cancers using PD-1 axis binding antagonists and anti-GPC3 antibodies
US12053534B2 (en) 2016-12-01 2024-08-06 Regeneron Pharmaceuticals, Inc. Radiolabeled anti-PD-L1 antibodies for immuno-PET imaging
US10736976B2 (en) 2016-12-01 2020-08-11 Regeneron Pharmaceuticals, Inc. Radiolabeled anti-PD-L1 antibodies for immuno-PET imaging

Also Published As

Publication number Publication date
WO2007047291A2 (fr) 2007-04-26
JP5303274B2 (ja) 2013-10-02
KR20080068023A (ko) 2008-07-22
HK1176076A1 (en) 2013-07-19
EP1933872B1 (fr) 2014-03-19
CN102850455B (zh) 2015-02-18
CN101287492A (zh) 2008-10-15
US9102739B2 (en) 2015-08-11
KR101397858B1 (ko) 2014-05-20
CA2624894C (fr) 2016-11-08
ES2470374T3 (es) 2014-06-23
AU2006304100C1 (en) 2013-08-29
EP1933872A2 (fr) 2008-06-25
IL190472A (en) 2017-01-31
BRPI0617412B8 (pt) 2022-08-30
US10118959B2 (en) 2018-11-06
JP2009511587A (ja) 2009-03-19
WO2007047291A3 (fr) 2007-06-21
AU2006304100A1 (en) 2007-04-26
IL190472A0 (en) 2008-11-03
CA2624894A1 (fr) 2007-04-26
US20080267979A1 (en) 2008-10-30
BRPI0617412B1 (pt) 2020-11-17
HK1120427A1 (en) 2009-04-03
CN102850455A (zh) 2013-01-02
CN101287492B (zh) 2013-06-12
BRPI0617412A2 (pt) 2011-07-26
US20150098941A1 (en) 2015-04-09
AU2006304100B2 (en) 2013-03-07

Similar Documents

Publication Publication Date Title
US10118959B2 (en) Anti-glypican-3 antibody
JP5715603B2 (ja) 抗グリピカン３抗体
CN105980557B (zh) 抗原结合能力根据化合物的浓度而变化的抗原结合分子及其文库
AU2005297772B2 (en) Anti-glypican 3 antibody having modified sugar chain
EP3130606A1 (fr) Molécule d'immunoactivation de liaison à un antigène
WO2005044857A1 (fr) Anticorps anti-cd47 humanise
AU2007332473A1 (en) Anti-Claudin-3 monoclonal antibody, and treatment and diagnosis of cancer using the same
CN103429737A (zh) 细胞毒诱导治疗剂
CA2691734A1 (fr) Anticorps anti-muc17
US20120321557A1 (en) Anti-icam3 antibody and use thereof
JP4331227B2 (ja) 抗グリピカン３抗体
JPWO2005034994A1 (ja) 固形腫瘍治療剤

Legal Events

Date Code Title Description
AS Assignment

Owner name: CHUGAI SEIYAKU KABUSHIKI KAISHA, JAPAN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:OKABE, HISAFUMI;SUGIMOTO, MASAMICHI;LIJIMA, SHIGEYUKI;AND OTHERS;REEL/FRAME:018371/0989

Effective date: 20060119

Owner name: XENCOR, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:LAZAR, GREGORY ALAN;DAHIYAT, BASSIL I.;REEL/FRAME:018371/0082

Effective date: 20051223

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载